The future prospects of pharmacogenetics in oral anticoagulation therapy

PubMed Central

Kamali, Farhad; Pirmohamed, Munir

2006-01-01

Coumarins are the mainstay of oral anticoagulation for the treatment and prophylaxis of thromboembolic disorders. They have a narrow therapeutic index and regular monitoring is therefore required to avoid serious adverse effects. There is wide interindividual variability in dosage requirements, which makes anticoagulation response unpredictable. Current dosing titrations are haphazard and inconvenient and poor initial control leads to morbidity, and occasional mortality, because of bleeding and further thromboembolism. Recent discoveries have helped to characterize the factors that contribute to the interindividual variability in responses to coumarins. Patient and environmental factors that affect anticoagulation response to coumarins include age, body size, dietary vitamin K status, concurrent disease and drug interactions. More recently, single nucleotide polymorphisms in the 2C9 isoform of cytochrome P450 (CYP2C9) and vitamin K epoxide reductase (VKOR) have been shown to make significant contributions to the variability in coumarin dosage requirements. Polymorphisms in other genes that mediate the actions of coumarins may also contribute to this variability. Racial and cultural differences influence dosage requirements, which can be explained, at least in part, by genetic and dietary factors. Incorporation of genetic and environmental factors could help in the prediction of more individualized loading and maintenance doses for safer anticoagulation therapy. PMID:16722840

Outcomes of anticoagulation therapy in patients with mental health conditions.

PubMed

Paradise, Helen T; Berlowitz, Dan R; Ozonoff, Al; Miller, Donald R; Hylek, Elaine M; Ash, Arlene S; Jasuja, Guneet K; Zhao, Shibei; Reisman, Joel I; Rose, Adam J

2014-06-01

Patients with mental health conditions (MHCs) experience poor anticoagulation control when using warfarin, but we have limited knowledge of the association between specific mental illness and warfarin treatment outcomes. To examine the relationship between the severity of MHCs and outcomes of anticoagulation therapy. Retrospective cohort analysis. We studied 103,897 patients on warfarin for 6 or more months cared for by the Veterans Health Administration during fiscal years 2007-2008. We identified 28,216 patients with MHCs using ICD-9 codes: anxiety disorders, bipolar disorder, depression, post-traumatic stress disorder, schizophrenia, and other psychotic disorders. Outcomes included anticoagulation control, as measured by percent time in the therapeutic range (TTR), as well as major hemorrhage. Predictors included different categories of MHC, Global Assessment of Functioning (GAF) scores, and psychiatric hospitalizations. Patients with bipolar disorder, depression, and other psychotic disorders experienced TTR decreases of 2.63 %, 2.26 %, and 2.92 %, respectively (p < 0.001), after controlling for covariates. Patients with psychotic disorders other than schizophrenia experienced increased hemorrhage after controlling for covariates [hazard ratio (HR) 1.24, p = 0.03]. Having any MHC was associated with a slightly increased hazard for hemorrhage (HR 1.19, p < 0.001) after controlling for covariates. Patients with specific MHCs (bipolar disorder, depression, and other psychotic disorders) experienced slightly worse anticoagulation control. Patients with any MHC had a slightly increased hazard for major hemorrhage, but the magnitude of this difference is unlikely to be clinically significant. Overall, our results suggest that appropriately selected patients with MHCs can safely receive therapy with warfarin.

European cardiac nurses' current practice and knowledge on anticoagulation therapy.

PubMed

Oterhals, Kjersti; Deaton, Christi; De Geest, Sabina; Jaarsma, Tiny; Lenzen, Mattie; Moons, Philip; Mårtensson, Jan; Smith, Karen; Stewart, Simon; Strömberg, Anna; Thompson, David R; Norekvål, Tone M

2014-06-01

Successful management of warfarin, new anti-thrombotic agents and self-monitoring devices requires that health care professionals effectively counsel and educate patients. Previous studies indicate that health care professionals do not always have the knowledge to provide patients with the correct information. The purpose of this study was to investigate European cardiovascular nurses' knowledge on the overall management of anticoagulation therapy and examine if this knowledge was influenced by level of education and years in clinical practice. A questionnaire including 47 items on practice patterns and knowledge on warfarin, new anticoagulants, warfarin-drug and warfarin-food interactions, and self-management of International Normalized Ratio (INR) was distributed to the attendants at a European conference in 2012. The response rate was 32% (n=206), of whom 84% reported having direct patient contact. Warfarin was the most common used oral anticoagulation in daily practice. One third offered their patients both patient self-testing and patient self-management of INR. The mean total score on the knowledge questions was 28±6 (maximum possible score 53). Nurses in direct patient care had a higher mean score (p=0.011). Knowledge on warfarin and medication-interactions were low, but knowledge on warfarin-diet interactions and how to advise patients on warfarin as somewhat better. European cardiac nurses need to improve their knowledge and practice patterns on oral anticoagulation therapy. This area of knowledge is important in order to deliver optimal care to cardiac patients and to minimise adverse effects of the treatment.

Spontaneous hemothorax following thrombolytic and anticoagulant therapy for massive pulmonary embolism.

PubMed

Wang, Chung-Cheng; Ng, Chip-Jin; Seak, Chen-Ken; Seak, Chen-June

2013-06-01

Massive spontaneous hemothorax following combined thrombolytic and anticoagulant therapy for pulmonary embolism(PE) is a rare event that is little documented in the literature. Here, we describe a rare case of spontaneous hemothorax in a 23-year-old woman with underlying systemic lupus erythematosus following combined administration of tissue plasminogen activator and low-molecular-weight heparin for massive PE. This report of our successful treatment of this case by video-assisted thoracoscopic thoracotomy demonstrates that although the occurrence is rare, massive hemothorax following anticoagulant and/or thrombolytic therapy for PE should be suspected if patients experience chest pain, dyspnea, or signs of anemia, and follow-up physical examination and hemogram should be performed to facilitate diagnosis of this life-threatening complication.

The future of anticoagulation clinics.

PubMed

Macik, B Gail

2003-01-01

Anticoagulation therapy is the foundation of treatment for thromboembolic disorders; and coumarin derivatives (warfarin in the United States) are the only orally administered anticoagulant medications currently available. Due to the expense and relative difficulties associated with this route of administration, parenteral drugs are not used routinely for long-term therapy, leaving warfarin as the anticoagulant of choice in the outpatient setting. The management of warfarin is problematic, however, due the nuances of its pharmacodynamic and pharmacokinetic profile and the requirement for frequent monitoring of blood levels. Although management by anticoagulation clinics is considered the gold standard for warfarin therapy, management by an anticoagulation clinic may not be the optimal option from a clinician's view and, in many cases, may not be an option at all. Anticoagulation clinics may impinge on the doctor-patient relationship. Difficulties of communication and reimbursement are not ameliorated by a specialty clinic. Innovations in warfarin management, including patient self-management and computerized dosing programs, are alternatives for improved care that are available with or without input by an anticoagulation service. New oral drugs on the horizon do not require the same intensity of monitoring and do not present the same pharmacodynamic problems associated with warfarin. Warfarin will become obsolete in the foreseeable future. If anticoagulation clinics continue, they must re-define their role as the major part of the workload, warfarin management, disappears. To adapt, clinics must strengthen and enhance their role as coordinators and educators, and less so, managers of anticoagulation therapy.

Pharmacogenomics of Anti-platelet and Anti-coagulation Therapy

PubMed Central

Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.

2013-01-01

Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323

Economic evaluation of strategies for restarting anticoagulation therapy after a first event of unprovoked venous thromboembolism.

PubMed

Monahan, M; Ensor, J; Moore, D; Fitzmaurice, D; Jowett, S

2017-08-01

Essentials Correct duration of treatment after a first unprovoked venous thromboembolism (VTE) is unknown. We assessed when restarting anticoagulation was worthwhile based on patient risk of recurrent VTE. When the risk over a one-year period is 17.5%, restarting is cost-effective. However, sensitivity analyses indicate large uncertainty in the estimates. Background Following at least 3 months of anticoagulation therapy after a first unprovoked venous thromboembolism (VTE), there is uncertainty about the duration of therapy. Further anticoagulation therapy reduces the risk of having a potentially fatal recurrent VTE but at the expense of a higher risk of bleeding, which can also be fatal. Objective An economic evaluation sought to estimate the long-term cost-effectiveness of using a decision rule for restarting anticoagulation therapy vs. no extension of therapy in patients based on their risk of a further unprovoked VTE. Methods A Markov patient-level simulation model was developed, which adopted a lifetime time horizon with monthly time cycles and was from a UK National Health Service (NHS)/Personal Social Services (PSS) perspective. Results Base-case model results suggest that treating patients with a predicted 1 year VTE risk of 17.5% or higher may be cost-effective if decision makers are willing to pay up to £20 000 per quality adjusted life year (QALY) gained. However, probabilistic sensitivity analysis shows that the model was highly sensitive to overall parameter uncertainty and caution is warranted in selecting the optimal decision rule on cost-effectiveness grounds. Univariate sensitivity analyses indicate variables such as anticoagulation therapy disutility and mortality risks were very influential in driving model results. Conclusion This represents the first economic model to consider the use of a decision rule for restarting therapy for unprovoked VTE patients. Better data are required to predict long-term bleeding risks during therapy in this

Healthcare resources and needs in anticoagulant therapy for patients with nonvalvular atrial fibrillation. SAMOA Study.

PubMed

Barrios, V; Egocheaga-Cabello, M I; Gállego-Culleré, J; Ignacio-García, E; Manzano-Espinosa, L; Martín-Martínez, A; Mateo-Arranz, J; Polo-García, J; Vargas-Ortega, D

2017-05-01

To determine, in the various medical specialties, the healthcare process for anticoagulated patients with nonvalvular atrial fibrillation, to determine the available and necessary resources and to identify potential areas of improvement in the care of these patients. We performed a cross-sectional survey of primary care and specialised physicians involved in the care of anticoagulated patients. The questionnaires referred to the healthcare process, the indication and prescription of anticoagulant therapy and the barriers and deficiencies present for these patients. A total of 893 physicians participated in the study, 437 of whom worked in primary care and 456 of whom were specialists (mostly cardiologists). Forty-two percent of the family doctors indicated that they assessed and prescribed anticoagulant therapy, and 66% performed the regular follow-up of these patients. In both healthcare settings, the physicians noted the lack of standardised protocols. There was also a lack of quality control in the treatment. The role of primary care in managing anticoagulated patients has grown compared with previous reports. The responses of the participating physicians suggest marked gaps in the standardisation of the healthcare process and several areas for improvement in these patients' follow-up. The promotion of training in direct-acting anticoagulant drugs remains pivotal. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Outcome after discontinuing anticoagulant therapy in women with venous thromboembolism during hormonal use.

PubMed

Blanco-Molina, Ángeles; Trujillo-Santos, Javier; Pesavento, Raffaele; Rosa, Vladimir; Falgá, Conxita; Tolosa, Carles; Mazzolai, Lucia; Sampériz, Ángel; Duce, Rita; Monreal, Manuel

2017-03-01

Whether women developing venous thromboembolism (VTE) while using hormonal therapy should be classified as having "unprovoked" or "provoked" VTE is controversial. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of symptomatic VTE recurrences after discontinuing anticoagulation in 3 subgroups of women aged ≤50years without cancer, pregnancy or puerperium: (1) those with hormonal therapy and no additional risk factors (hormonal users only); (2) those with unprovoked VTE; and (3) those with additional risk factors, with or without hormonal therapy. As of March 2016, 1513 women had been followed-up for at least one month after discontinuing anticoagulation. Of these, 654 (43%) were hormonal users only, 390 (26%) had unprovoked VTE and 469 (31%) had transient risk factors with or without hormonal therapy. After discontinuing anticoagulation, the rate of VTE recurrences in women with hormonal use only (2.44 per 100 patient-years; 95% CI: 1.53-3.69) was significantly lower than in those with unprovoked VTE (6.03; 95% CI: 3.97-8.77) and similar to those with transient risk factors (2.58; 95% CI: 1.50-4.13). Interestingly, the rate of VTE recurrences presenting as pulmonary embolism in women with hormonal use only (0.55 per 100 patient-years; 95% CI: 0.18-1.29) was similar to those with transient risk factors (0.46; 95% CI: 0.09-1.33) and 4-fold lower than in women with unprovoked VTE (2.23; 95% CI: 1.07-4.10). After discontinuing anticoagulation, the rate of VTE recurrences in hormonal users only was significantly lower than in women with unprovoked VTE and similar to the rate in women with additional risk factors. © 2017 Elsevier Ltd. All rights reserved.

Impact of anticoagulation therapy on valve haemodynamic deterioration following transcatheter aortic valve replacement.

PubMed

Del Trigo, María; Muñoz-García, Antonio J; Latib, Azeem; Auffret, Vincent; Wijeysundera, Harindra C; Nombela-Franco, Luis; Gutierrez, Enrique; Cheema, Asim N; Serra, Vicenç; Amat-Santos, Ignacio J; Kefer, Joelle; Benitez, Luis Miguel; Leclercq, Florence; Mangieri, Antonio; Le Breton, Hervé; Jiménez-Quevedo, Pilar; Garcia Del Blanco, Bruno; Dager, Antonio; Abdul-Jawad Altisent, Omar; Puri, Rishi; Pibarot, Philippe; Rodés-Cabau, Josep

2018-05-01

To evaluate the changes in transvalvular gradients and the incidence of valve haemodynamic deterioration (VHD) following transcatheter aortic valve replacement (TAVR), according to use of anticoagulation therapy. This multicentre study included 2466 patients (46% men; mean age 81±7 years) who underwent TAVR with echocardiography performed at 12-month follow-up. Anticoagulation therapy was used in 707 patients (28.7%) following TAVR (AC group). A total of 663 patients received vitamin K antagonists, and 44 patients received direct oral anticoagulants. A propensity score matching analysis was performed to adjust for intergroup (AC vs non-AC post-TAVR) differences. A total of 622 patients per group were included in the propensity-matched analysis. VHD was defined as a ≥10 mm Hg increase in the mean transprosthetic gradient at follow-up (vs hospital discharge). The mean clinical follow-up was 29±18 months. The mean transvalvular gradient significantly increased at follow-up in the non-AC group within the global cohort (P=0.003), whereas it remained stable over time in the AC group (P=0.323). The incidence of VHD was significantly lower in the AC group (0.6%) compared with the non-AC group (3.7%, P<0.001), and these significant differences remained within the propensity-matched populations (0.6% vs 3.9% in the AC and non-AC groups, respectively, P<0.001). The occurrence of VHD did not associate with an increased risk of all-cause death (P=0.468), cardiovascular death (P=0.539) or stroke (P=0.170) at follow-up. The lack of anticoagulation therapy post-TAVR was associated with significant increments in transvalvular gradients and a greater risk of VHD. VHD was subclinical in most cases and did not associate with major adverse clinical events. Future randomised trials are needed to determine if systematic anticoagulation therapy post-TAVR would reduce the incidence of VHD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article

[Anticoagulation and peripartum management].

PubMed

Philippe, A; Ruivard, M; Auclair, C; Accoceberry, M; Bonnin, M; Pouly, J-L; Lémery, D; Philippe, P; Gallot, D

2015-03-01

To compare peripartum management of anticoagulated patients concerning locoregional analgesia, post-partum hemorrhage and thrombotic events according to planified interruption or not of antithrombotic therapy. We conducted a single tertiary care center retrospective study of all deliveries associated with antithrombotic therapy from January 2005 to September 2011. We identified 120 cases with prophylactic (71%) or curative (29%) anticoagulation. Two thrombotic events occurred. In case of curative therapy, the use of locoregional analgesia was lower (P<0.0001) and post-partum hemorrhage occurred more frequently (P=0.07) compared to prophylactic therapy. According to planified interruption or not of antithrombotic therapy, we observed a more prolonged duration of therapeutic interruption before delivery (55.6h±63.3 vs 26.4 h±11.6, P<0.0001), higher use of locoregional analgesia (83% vs 71%, P=0.02) but no difference concerning cesarean rate (35% vs 39%, P=0.8) or post-partum hemorrhage (13% vs 14%, P=0.9). In case of curative anticoagulation, plannified interruption favours the use of perimedullar analgesia after 24hour delay. In case of preventive anticoagulation, plannified interruption appears unnecessary as the 12hour delay is easier to reach. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Risks and benefits of citrate anticoagulation for continuous renal replacement therapy.

PubMed

Shum, H P; Yan, W W; Chan, T M

2015-04-01

Heparin, despite its significant side-effects, is the most commonly used anticoagulant for continuous renal replacement therapy in critical care setting. In recent years, citrate has gained much popularity by improving continuous renal replacement therapy circuit survival and decreasing blood transfusion requirements. However, its complex metabolic consequences warrant modification in the design of the citrate-based continuous renal replacement therapy protocol. With thorough understanding of the therapeutic mechanism of citrate, a simple and practicable protocol can be devised. Citrate-based continuous renal replacement therapy can be safely and widely used in the clinical setting with appropriate clinical staff training.

Safety of percutaneous nephrolithotomy in patients on chronic anticoagulant or antiplatelet therapy.

PubMed

Fernández-Baltar, C; Pérez-Fentes, D; Sánchez-García, J F; García-Freire, C

2018-01-22

In developed countries, the incidence of cardiovascular disease is increasing, therefore, anticoagulant and antiplatelet drugs are a widespread treatment nowadays. Percutaneous nephrolithotomy (PNL) is the first-line treatment for large or complex stones (> 2 cm) and remains an alternative for the smaller ones. The objective of this study is to analyze whether PNL surgery is a safe procedure in patients under a treatment discontinuation protocol for anticoagulant or antiplatelet therapies. We retrospectively studied 301 patients who underwent PNL in our hospital between 2008 and 2016 and identified 46 patients on chronic antiplatelet or anticoagulation treatment. With respect to PNL outcomes, the stone-free rate was similar (78 vs 74%, p = 0.762) in both groups, without any significant differences in the overall postoperative complications (17 vs 26%, p = 0.203). The incidence of hemorrhagic complications was similar between groups (12 vs 9%, p = 0.492), as demonstrated by the mean drop in hemoglobin (Hb), which was comparable in both cohorts (2.2 ± 1.3 vs 2.0 ± 1.4 p = 0.270) and the blood transfusion rate (14% in group A and 8% in group B, p = 0.205). No thromboembolic events were found within the year after the PNL procedure. PNL is a safe and effective intervention in patients under a treatment discontinuation protocol for anticoagulant or antiplatelet therapies. Although our study demonstrates the feasibility of this protocol, new scientific evidence aims to stratify the thromboembolic and bleeding risk of each patient to individualize the perioperative management thereafter.

Upsetting the apple cart: a community anticoagulation clinic survey of life event factors that undermine safe therapy.

PubMed

Edmundson, Sarah; Stuenkel, Diane L; Connolly, Phyllis M

2005-09-01

Anticoagulation therapy is a life-enhancing therapy for patients who are at risk for embolic events secondary to atrial fibrillation, valve replacement, and other comorbidities. Clinicians are motivated to decrease the amount of time that patients are either under- or over-anticoagulated, common conditions that decrease patient safety at either extreme. The primary purpose of this descriptive study was to examine the relationship between personal life event factors as measured by Norbeck's Life Events Questionnaire, core demographics such as age and income, and anticoagulation regulation. Although many factors affect anticoagulation therapy, the precise impact of life events, positive or negative, is unknown. The salient findings of this study (n = 202) showed a small, though statistically significant, inverse relationship (r = -0.184, P < .01) between negative life events and decreased time within therapeutic international normalized ratio. Total Life Event scores showed a statistically significant inverse relationship (r = -0.159, P < .05) to international normalized ratio time within therapeutic level. Lower income was inversely associated with higher negative Life Event scores (r = -0.192, P < .01). The findings demonstrate the need for strategies that address the potential impact of life events in conjunction with coexisting screening measures used in anticoagulation clinics. Implications for this study are limited by lack of methodology documenting concurrent social support factors and limitations of the research tool to reflect life event issues specific to outpatient seniors.

Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy.

PubMed

Maas, Angela H E M; Euler, Mia von; Bongers, Marlies Y; Rolden, Herbert J A; Grutters, Janneke P C; Ulrich, Lian; Schenck-Gustafsson, Karin

2015-12-01

A growing number of premenopausal women are currently using antithrombotic and/or (dual) antiplatelet therapy for various cardiovascular indications. These may induce or exacerbate abnormal uterine bleeding and more awareness and knowledge among prescribers is required. Heavy and irregular menstrual bleeding is common in women in their forties and may have a variety of underlying causes that require different treatment options. Thus using anticoagulants in premenopausal women demands specific expertise and close collaboration between cardiovascular physicians and gynecologists. In this article we summarize the scope of the problem and provide practical recommendations for the care for young women taking anticoagulants and/or (dual) antiplatelet therapy. We also recommend that more safety data on uterine bleeding with novel anticoagulants in premenopausal women should be obtained. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Using Artificial Intelligence to Reduce the Risk of Nonadherence in Patients on Anticoagulation Therapy.

PubMed

Labovitz, Daniel L; Shafner, Laura; Reyes Gil, Morayma; Virmani, Deepti; Hanina, Adam

2017-05-01

This study evaluated the use of an artificial intelligence platform on mobile devices in measuring and increasing medication adherence in stroke patients on anticoagulation therapy. The introduction of direct oral anticoagulants, while reducing the need for monitoring, have also placed pressure on patients to self-manage. Suboptimal adherence goes undetected as routine laboratory tests are not reliable indicators of adherence, placing patients at increased risk of stroke and bleeding. A randomized, parallel-group, 12-week study was conducted in adults (n=28) with recently diagnosed ischemic stroke receiving any anticoagulation. Patients were randomized to daily monitoring by the artificial intelligence platform (intervention) or to no daily monitoring (control). The artificial intelligence application visually identified the patient, the medication, and the confirmed ingestion. Adherence was measured by pill counts and plasma sampling in both groups. For all patients (n=28), mean (SD) age was 57 years (13.2 years) and 53.6% were women. Mean (SD) cumulative adherence based on the artificial intelligence platform was 90.5% (7.5%). Plasma drug concentration levels indicated that adherence was 100% (15 of 15) and 50% (6 of 12) in the intervention and control groups, respectively. Patients, some with little experience using a smartphone, successfully used the technology and demonstrated a 50% improvement in adherence based on plasma drug concentration levels. For patients receiving direct oral anticoagulants, absolute improvement increased to 67%. Real-time monitoring has the potential to increase adherence and change behavior, particularly in patients on direct oral anticoagulant therapy. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02599259. © 2017 American Heart Association, Inc.

The Best Anticoagulation Therapy in Multiple-Trauma Patients with Mechanical Heart Valves: Evaluation of Latest Guidelines and Studies.

PubMed

Moeinipour, Aliasghar; Zarifian, Ahmadreza; Sheikh Andalibi, Mohammad Sobhan; Shamloo, Alireza Sepehri; Ahmadabadi, Ali; Amouzeshi, Ahmad; Hoseinikhah, Hamid

2015-12-22

It is common practice for patients with prosthetic cardiac devices, especially heart valve prosthesis, arterial stents, defibrillators, and pacemaker devices, to use anticoagulation treatment. When these patients suffer from multiple trauma after motor vehicle accidents, the best medical management for this challenging position is mandatory. This strategy should include a rapid diagnosis of all possible multiple organ injuries, with special attention to anticoagulation therapy so as to minimize the risk of thromboembolism complication in prosthetic devices. In this review, we describe the best medical management for patients with multiple trauma who use anticoagulants after heart valve replacement. We searched electronic databases PubMed/Medline, Scopus, Embase, and Google Scholar using the following terms: anticoagulant, warfarin, heparin, and multiple trauma. Also, similar studies suggested by the databases were included. Non-English articles were excluded from the review. For patients who use anticoagulation therapy, teamwork between cardiac surgeons, general surgeons, anesthesiologists, and cardiologists is essential. For optimal medical management, multiple consults between members of this team is mandatory for rapid diagnosis of all possible damaged organs, with special attention to the central nervous system, chest, and abdominal traumas. With this strategy, it is important to take note of anticoagulation drugs to minimize the risk of thromboembolism complications in cardiac devices. The best anticoagulant agents for emergency operations in patients with multiple trauma who are using an anticoagulant after heart valve replacement are fresh frozen plasma (FFP) and prothrombin complex concentrates (PCC).

Patients' understanding of anticoagulant therapy in a multiethnic population

PubMed Central

Nadar, Sunil; Begum, Nazneen; Kaur, Bhupinder; Sandhu, Sukhpreet; Lip, Gregory Y H

2003-01-01

To investigate whether knowledge and perceptions of antithrombotic therapy differ between ethnic groups in the UK, we conducted a cross-sectional questionnaire survey of patients attending anticoagulation clinics in three Birmingham teaching hospitals. 180 consecutive patients were recruited—135 white European, 29 Indo-Asian, 16 Afro-Caribbean. The average knowledge score was 5.5 out of 9, with no significant differences between the groups. Indo-Asians were significantly less likely than the other groups to know the name of the anticoagulant they were taking (warfarin) and Afro-Caribbeans to know the condition for which they were being anticoagulated. Few patients of any group were able to specify more than one side-effect of warfarin or the dose they were on. In logistic regression analysis the factors associated with a low score were age >61 years, having been born outside the UK, and the perception of difficulty in comprehension. Nearly half the Indo-Asians felt unable to understand what was said to them in the clinic, and 62% expressed a preference for a doctor of the same ethnic group. Although there were no significant between-group differences, this study points to gaps in the knowledge of patients from ethnic minorities and to deficiencies in the provision of information. In patient education, these groups should receive special attention. PMID:12668704

Is Endoscopic Therapy Safe for Upper Gastrointestinal Bleeding in Anticoagulated Patients With Supratherapeutic International Normalized Ratios?

PubMed

Shim, Choong Nam; Chung, Hyun Soo; Park, Jun Chul; Shin, Sung Kwan; Lee, Sang Kil; Lee, Yong Chan; Kim, Ha Yan; Kim, Dong Wook; Lee, Hyuk

2016-01-01

The management of upper gastrointestinal bleeding (UGIB) in anticoagulated patients with supratherapeutic international normalized ratios (INRs) presents a challenge. The purpose of the study was to evaluate the safety of endoscopic therapy for UGIB in anticoagulated patients with supratherapeutic INR in terms of rebleeding and therapeutic outcomes. One hundred ninety-two anticoagulated patients who underwent endoscopic treatment for UGIB were enrolled in the study. Patients were divided into 2 groups based on the occurrence of rebleeding within 30 days of the initial therapeutic endoscopy: no-rebleeding group (n = 168) and rebleeding group (n = 24). The overall rebleeding rate was 12.5%. Bleeding from gastric cancer and bleeding at the duodenum were significantly related to rebleeding in a univariate analysis. Multivariate analysis determined that presenting symptoms other than melena (hematemesis, hematochezia, or others) (odds ratio, 3.93; 95% confidence interval, 1.44-10.76) and bleeding from gastric cancer (odds ratio, 6.10; 95% confidence interval, 1.27-29.25) were significant factors predictive of rebleeding. Supratherapeutic INR at the time of endoscopic therapy was not significantly associated with rebleeding in either univariate or multivariate analysis. Significant differences in bleeding-related mortality, additional intervention to control bleeding, length of hospital stay, and transfusion requirements were revealed between the rebleeding and no-rebleeding groups. There were no significant differences in therapeutic outcomes between patients with INR within the therapeutic range and those with supratherapeutic INR. Supratherapeutic INR at the time of endoscopic therapy did not change rebleeding and therapeutic outcomes. Thus, we should consider endoscopic therapy for UGIB in anticoagulated patients, irrespective of INR at the time of endoscopic therapy.

Posttraumatic gastric wall hematoma in a patient under anticoagulant therapy. Case report and literature review.

PubMed

Mânzat Saplacan, Roberta Maria; Catinean, Adrian; Manole, Simona; Valean, Simona Doina; Chira, Romeo Ioan; Mircea, Petru Adrian

2011-06-01

We report the clinical observation of a 58-year old patient who presented with upper abdominal pain and a small ecchymosis located in the umbilical area. Personal history of the patient revealed ischemic heart disease and chronic atrial fibrillation. He was under treatment with oral anticoagulants (coumarins). The clinical data and especially the imaging investigations led to a diagnosis of gastric wall hematoma, possibly occurring post-traumatically in a patient under anticoagulant treatment. A conservative therapeutic approach was adopted and ultrasound surveillance. After 6 months the gastric parietal collection manifested complete resorption, spontaneously. In relation to the case presentation, we also discuss some issues on the frequency, diagnosis and therapeutic attitude in this rare complication of anticoagulant therapy.

Impact of optimal anticoagulation therapy on chronic venous ulcer healing in thrombophilic patients with post-thrombotic syndrome.

PubMed

Hinojosa, C A; Olivares-Cruz, S; Laparra-Escareno, H; Sanchez-Castro, S; Tamayo-Garcia, B; Anaya-Ayala, J E

2016-12-02

Post-thrombotic syndrome (PTS) is the long-term sequelae of deep venous thrombosis (DVT). PTS clinical manifestations include chronic leg pain, oedema, lipodermatosclerosis and ulcers. The objective of this study is to determine in patients with documented history of thrombophilias and DVT whether the number of previous thrombotic events and optimal anticoagulation therapy are associated with the time to venous ulcer healing following the start of compression therapy. Retrospective analysis performed in thrombophilic patients under the age of 50 years old with chronic venous ulcers secondary to DVT at the wound clinic in the National Institute of Medical Sciences and Nutrition 'Salvador Zubirán ' in Mexico City. Variables such as the number or episodes of thrombotic events, type of hypercoagulable disorder, optimal anticoagulation therapy with Warfarin monitored by therapeutic International Normalised Ratio (INR) (2-3) and compliance to compression therapy were examined. Patients that underwent superficial or perforator vein interruption or endovascular recanalisation of deep veins were excluded from the study. From a database of 29 patients with chronic venous ulcers followed in our clinic from January 1992 to September 2012, only 13 patients (61% female) met the inclusion criteria. Mean age±standard deviation (SD) was 32±12 years old. Of these, seven (54%) patients with suboptimal INR presented with an average of two previous thrombotic events and the remaining six (46%) patients with optimal INR only one event (p=0.28), the mean time to the clinical manifestation of a venous ulcer after the first episode of DVT was 39 months (range: 12-72) for patients with suboptimal INR and 82 months (range: 12-216) for those with optimal anticoagulation therapy (p=0.11). During the mean follow-up period of 52 months, all patients in optimal anticoagulation healed their ulcer; their mean time for wound healing was 44 months (range: 4-102). In the suboptimal INR group, only

A surgeon's guide to anticoagulant and antiplatelet medications part one: warfarin and new direct oral anticoagulant medications

PubMed Central

McBeth, Paul B; Weinberg, Jordan A; Sarani, Babak; Yeung, Louise Y Y; May, Addison K

2016-01-01

An increasing number of potent antiplatelet and anticoagulant medications are being used for the long-term management of cardiac, cerebrovascular, and peripheral vascular conditions. Management of these medications in the perioperative and peri-injury settings can be challenging for surgeons, mandating an understanding of these agents and the risks and benefits of various management strategies. In this two-part review, agents commonly encounter by surgeons in the perioperative and peri-injury settings are discussed and management strategies for patients on long-term antiplatelet and anticoagulant therapy reviewed. In part I, we review warfarin and the new direct oral anticoagulants. In part II, we review antiplatelet agents and assessment of platelet function and the perioperative management of long-term anticoagulant and antiplatelet therapy. PMID:29767647

Anticoagulation management in the ambulatory surgical setting.

PubMed

Eisenstein, Diana Hill

2012-04-01

Many people receiving maintenance anticoagulation therapy require surgery each year in ambulatory surgery centers. National safety organizations focus attention toward improving anticoagulation management, and the American College of Chest Physicians has established guidelines for appropriate anticoagulation management to balance the risk of thromboembolism when warfarin is discontinued with the risk of bleeding when anticoagulation therapy is maintained. The guidelines recommend that patients at high or moderate risk for thromboembolism should be bridged with subcutaneous low-molecular-weight heparin or IV unfractionated heparin with the interruption of warfarin, and low-risk patients may require subcutaneous low-molecular-weight heparin or no bridging with the interruption of warfarin. The guidelines recommend the continuation of warfarin for patients who are undergoing minor dermatologic or dental procedures or cataract removal. The literature reveals, however, that there is not adequate adherence to these recommendations and guidelines. Management of anticoagulation therapy by a nurse practitioner may improve compliance and safety in ambulatory surgery centers. Copyright © 2012 AORN, Inc. Published by Elsevier Inc. All rights reserved.

What NPs need to know about anticoagulation therapy.

PubMed

Gay, Sarah E; Munaco, Sandra

2012-10-10

Venous thromboembolism (VTE) refers to pulmonary embolism and deep venous thrombosis. Anticoagulation is the cornerstone of management for patients with VTE. This review will discuss current anticoagulation guidelines.

Surgeon's guide to anticoagulant and antiplatelet medications part two: antiplatelet agents and perioperative management of long-term anticoagulation

PubMed Central

Yeung, Louise Y Y; Sarani, Babak; Weinberg, Jordan A; McBeth, Paul B; May, Addison K

2016-01-01

An increasing number of potent antiplatelet and anticoagulant medications are being used for the long-term management of cardiac, cerebrovascular, and peripheral vascular conditions. Management of these medications in the perioperative and peri-injury settings can be challenging for surgeons, mandating an understanding of these agents and the risks and benefits of various management strategies. In this two part review, agents commonly encountered by surgeons in the perioperative and peri-injury settings are discussed and management strategies for patients on long-term antiplatelet and anticoagulant therapy reviewed. In part one, we review warfarin and the new direct oral anticoagulants. In part two, we review antiplatelet agents and assessment of platelet function and the perioperative management of long-term anticoagulation and antiplatelet therapy. PMID:29767644

Non-invasive MR-guided HIFU Therapy of TSC-Associated Renal Angiomyolipomas

DTIC Science & Technology

2012-07-01

AD_________________ Award Number: W81XWH-11-1-0299 TITLE: Non- invasive MR-guided HIFU Therapy...3. DATES COVERED 1 July 2011-30 June 2012 4. TITLE AND SUBTITLE Non- invasive MR-guided HIFU Therapy of TSC-Associated Renal Angiomyolipomas 5a... focused on technological development for thermal ablation in mice. Our goal was to establish a small-animal MR-guided HIFU experimental system that

[New oral anticoagulant drugs].

PubMed

Berkovits, Alejandro; Aizman, Andrés; Zúñiga, Pamela; Pereira, Jaime; Mezzano, Diego

2011-10-01

Thromboembolic disease (TED) is the leading cause of morbidity and mortality worldwide. The hallmark of oral long-term anticoagulant therapy has been the use of vitamin K antagonists, whose anticoagulant effect is exerted inhibiting vitamin K epoxide reductase. Warfarin and acenocoumarol are the most commonly used. In the last five years several new drugs for long term anticoagulation have been developed, which can inhibit single clotting factors with the purpose of improving drug therapeutic range and, ideally, minimizing bleeding risks. This review addresses the state of the art on the clinical use of inhibitors of activated factor X and thrombin.

[Concepts in anticoagulant therapy - past, present, and future].

PubMed

Graf, L

2012-11-01

The understanding of the clotting system emerged in parallel to the development of anticoagulants. In contrast to vitamin K-antagonists and heparins that where discovered by chance, new anticoagulants have been systematically designed to specifically inhibit single clotting factors. Both clotting factors Xa (FXa) and thrombin play a crucial role within the new cell-based model of hemostasis. Thus it is obvious that FXa and thrombin turned out to be ideal targets for anticoagulation. The proof of the concept of selective inhibition of thrombin and FXa has been provided by hirudin and fondaparinux, respectively. By now, a whole group of new oral anticoagulants has been licensed: the direct FXa-inhibitors rivaroxaban, apixaban, and edoxaban as well as the direct thrombin dabigatran etexilate. Furthermore, a bundle of FXa- and thrombin-inhibitors that differ from the so far licensed products mainly in pharmacokinetics are in an advanced phase of development. A further innovative concept of anticoagulation that entered its clinical phase of development is the inhibition of factor VIII. Other new concepts such as inhibition of initiation of coagulation by blocking factor VIIa, inhibition of contact factor XII, or inhibition of factor IX are in an early phase of development.

Monitoring of anticoagulant therapy in heart disease: considerations for the current assays.

PubMed

Boroumand, Mohammadali; Goodarzynejad, Hamidreza

2010-01-01

Clinicians should be aware of new developments to familiarize themselves with pharmacokinetic and pharmacodynamic characteristics of new anticoagulant agents to appropriately and safely use them. For the moment, cardiologists and other clinicians also require to master currently available drugs, realizing the mechanism of action, side effects, and laboratory monitoring to measure their anticoagulant effects. Warfarin and heparin have narrow therapeutic window with high inter- and intra-patient variability, thereby the use of either drug needs careful laboratory monitoring and dose adjustment to ensure proper antithrombotic protection while minimizing the bleeding risk. The prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are laboratory tests commonly used to monitor warfarin and heparin, respectively. These two tests depend highly on the combination of reagent and instrument utilized. Results for a single specimen tested in different laboratories are variable; this is mostly attributable to the specific reagents and to a much lesser degree to the instrument used. The PT stands alone as the single coagulation test that has undergone the most extensive attempt at assay standardization. The international normalized ratio (INR) was introduced to "normalize" all PT reagents to a World Health Organization (WHO) reference thromboplastin preparation standard, such that a PT measured anywhere in the world would result in an INR value similar to that which would have been achieved had the WHO reference thromboplastin been utilized. However, INRs are reproducible between laboratories for only those patients who are stably anticoagulated with vitamin K antagonists (VKAs) (i.e., at least 6 weeks of VKA therapy), and are not reliable or reproducible between laboratories for patients for whom VKA therapy has recently been started or any other clinical conditions associated with a prolonged PT such as liver disease, disseminated intravascular coagulation

Anticoagulation Bridge Therapy in Patients with Atrial Fibrillation: Recent Updates Providing a Rebalance of Risk and Benefit.

PubMed

Garwood, Candice L; Korkis, Bianca; Grande, Domenico; Hanni, Claudia; Morin, Amy; Moser, Lynette R

2017-06-01

In 2011 we reviewed clinical updates and controversies surrounding anticoagulation bridge therapy in patients with atrial fibrillation (AF). Since then, options for oral anticoagulation have expanded with the addition of four direct oral anticoagulant (DOAC) agents available in the United States. Nonetheless, vitamin K antagonist (VKA) therapy continues to be the treatment of choice for patients who are poor candidates for a DOAC and for whom bridge therapy remains a therapeutic dilemma. This literature review identifies evidence and guideline and consensus statements from the last 5 years to provide updated recommendations and insight into bridge therapy for patients using a VKA for AF. Since our last review, at least four major international guidelines have been updated plus a new consensus document addressing bridge therapy was released. Prospective trials and one randomized controlled trial have provided guidance for perioperative bridge therapy. The clinical trial data showed that bridging with heparin is associated with a significant bleeding risk compared with not bridging; furthermore, data suggested that actual perioperative thromboembolic risk may be lower than previously estimated. Notably, patients at high risk for stroke have not been adequately represented. These findings highlight the importance of assessing thrombosis and bleeding risk before making bridging decisions. Thrombosis and bleeding risk tools have emerged to facilitate this assessment and have been incorporated into guideline recommendations. Results from ongoing trials are expected to provide more guidance on safe and effective perioperative management approaches for patients at high risk for stroke. © 2017 Pharmacotherapy Publications, Inc.

Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant.

PubMed

Glueck, Charles J; Lee, Kevin; Prince, Marloe; Jetty, Vybhav; Shah, Parth; Wang, Ping

2016-01-01

When exogenous testosterone or treatments to elevate testosterone (human chorionic gonadotropin [HCG] or Clomid) are prescribed for men who have antecedent thrombophilia, deep venous thrombosis and pulmonary embolism often occur and may recur despite adequate anticoagulation if testosterone therapy is continued. A 55-year-old white male was referred to us because of 4 thrombotic events, 3 despite adequate anticoagulation over a 5-year period. We assessed interactions between thrombophilia, exogenous testosterone therapy, and recurrent thrombosis. In 2009, despite low-normal serum testosterone 334 ng/dL (lower normal limit [LNL] 300 ng/dL), he was given testosterone (TT) cypionate (50 mg/week) and human chorionic gonadotropin (HCG; 500 units/week) for presumed hypogonadism. Ten months later, with supranormal serum T (1385 ng/dL, upper normal limit [UNL] 827 ng/dL) and estradiol (E2) 45 pg/mL (UNL 41 pg/mL), he had a pulmonary embolus (PE) and was then anticoagulated for 2 years (enoxaparin, then warfarin). Four years later, on TT-HCG, he had his first deep venous thrombosis (DVT). TT was stopped and HCG continued; he was anticoagulated (enoxaparin, then warfarin, then apixaban, then fondaparinux). One year after his first DVT, on HCG, still on fondaparinux, he had a second DVT (5/315), was anticoagulated (enoxaparin + warfarin), with a Greenfield filter placed, but 8 days later had a second PE. Thrombophilia testing revealed the lupus anticoagulant. After stopping HCG, and maintained on warfarin, he has been free of further DVT-PE for 9 months. When DVT-PE occur on TT or HCG, in the presence of thrombophilia, TT-HCG should be stopped, lest DVT-PE reoccur despite concurrent anticoagulation.

Health literacy and warfarin therapy at two anticoagulation clinics in Brazil

PubMed Central

Martins, Maria Auxiliadora Parreiras; Costa, Josiane Moreira; Mambrini, Juliana Vaz de Melo; Ribeiro, Antonio Luiz Pinho; Benjamin, Emelia J; Brant, Luisa Campos Caldeira; Paasche-Orlow, Michael K; Magnani, Jared W

2017-01-01

Objective Health literacy has been related to health-related conditions and health outcomes. Studies examining the association of health literacy and anticoagulation have had variable results. We sought to investigate the relations of health literacy and percentage of time in therapeutic range (TTR) in a vulnerable Brazilian cohort at two hospital-based anticoagulation clinics. Methods We measured health literacy with the Short Assessment of Health Literacy for Portuguese-speaking Adults (SAHLPA-18) in 2015–2016. We identified the demographic and clinical characteristics associated with health literacy and related health literacy to TTR. Results We enrolled 422 adults prescribed chronic warfarin therapy in our observational study (median age 62.1 years; 58.8% women; monthly income $200.00). The prevalence of inadequate health literacy (score 0–14 points) was 72.3% with a median score of 12 (quartiles, Q1=10; Q3=15) on the SAHLPA-18. The median TTR was 66.1%. In the multivariable logistic analysis, cognitive impairment and assistance with taking warfarin were associated with inadequate health literacy. Prosthetic heart valves and more school years were associated with adequate health literacy. Our analyses showed no significant relation between health literacy and TTR, analysing health literacy as a categorical (adjusted OR 1.05; 95% CI 0.65 to 1.70) or continuous variable (Spearman’s coefficient 0.02; p=0.70). Conclusions Inadequate health literacy was highly prevalent in this impoverished Brazilian cohort receiving anticoagulation with warfarin. However, we did not identify an association between health literacy and TTR. Future investigations may consider the systemic factors that contribute towards successful anticoagulation outcomes for vulnerable patient cohorts with inadequate health literacy. PMID:28258243

Comparison between videotape and personalized patient education for anticoagulant therapy.

PubMed

Stone, S; Holden, A; Knapic, N; Ansell, J

1989-07-01

To assess the effectiveness of videotape patient education, 22 patients were randomized to receive either videotape or personalized teaching for oral anticoagulant (warfarin) therapy. Both groups scored significantly higher on a questionnaire designed to assess knowledge gained after instruction, with no significant difference between the two groups. Videotape instruction required substantially less nursing time. A second questionnaire assessed patient satisfaction with respect to both methods, which were rated equally effective and worthwhile. Videotape teaching is an effective and well-accepted alternative form of patient education requiring significantly less personnel time.

Health literacy and warfarin therapy at two anticoagulation clinics in Brazil.

PubMed

Martins, Maria Auxiliadora Parreiras; Costa, Josiane Moreira; Mambrini, Juliana Vaz de Melo; Ribeiro, Antonio Luiz Pinho; Benjamin, Emelia J; Brant, Luisa Campos Caldeira; Paasche-Orlow, Michael K; Magnani, Jared W

2017-07-01

Health literacy has been related to health-related conditions and health outcomes. Studies examining the association of health literacy and anticoagulation have had variable results. We sought to investigate the relations of health literacy and percentage of time in therapeutic range (TTR) in a vulnerable Brazilian cohort at two hospital-based anticoagulation clinics. We measured health literacy with the Short Assessment of Health Literacy for Portuguese-speaking Adults (SAHLPA-18) in 2015-2016. We identified the demographic and clinical characteristics associated with health literacy and related health literacy to TTR. We enrolled 422 adults prescribed chronic warfarin therapy in our observational study (median age 62.1 years; 58.8% women; monthly income $200.00). The prevalence of inadequate health literacy (score 0-14 points) was 72.3% with a median score of 12 (quartiles, Q1=10; Q3=15) on the SAHLPA-18. The median TTR was 66.1%. In the multivariable logistic analysis, cognitive impairment and assistance with taking warfarin were associated with inadequate health literacy. Prosthetic heart valves and more school years were associated with adequate health literacy. Our analyses showed no significant relation between health literacy and TTR, analysing health literacy as a categorical (adjusted OR 1.05; 95% CI 0.65 to 1.70) or continuous variable (Spearman's coefficient 0.02; p=0.70). Inadequate health literacy was highly prevalent in this impoverished Brazilian cohort receiving anticoagulation with warfarin. However, we did not identify an association between health literacy and TTR. Future investigations may consider the systemic factors that contribute towards successful anticoagulation outcomes for vulnerable patient cohorts with inadequate health literacy. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Noninvasive MR-Guided HIFU Therapy of TSC-Associated Renal Angiomyolipomas

DTIC Science & Technology

2014-09-01

of TSC-Associated Renal Angiomyolipomas PRINCIPAL INVESTIGATOR: Yu Li CONTRACTING ORGANIZATION: Children’s Hospital, REPORT DATE...TITLE AND SUBTITLE Non nvasive MR- uided HIFU Therapy of TSC-Associated Renal Angiomyolipomas 5a. CONTRACT NUMBER 5b. GRANT NUMBER 6. AUTHOR...investigation, we are reformatting our research and planning for another effort to investigate MR-guided HIFU therapy of TSC-related renal angiomyolipomas in

Effects of Marine Fish Oils on the Anticoagulation Status of Patients Receiving Chronic Warfarin Therapy.

PubMed

Bender; Kraynak; Chiquette; Linn; Clark; Bussey

1998-07-01

The purpose of this placebo-controlled, randomized, double-blinded, parallel study was to determine the existence and magnitude of effect of various doses of fish oil supplements on International Normalized Ratio (INR) determinations in patients receiving chronic warfarin therapy. Patients from anticoagulation clinics from both the Brady Green Community Health Center and Audie L. Murphy Veterans Administration in San Antonio, Texas were enrolled in the study. The enrolled subjects included 5 males and 11 females, all of whom were receiving chronic warfarin therapy for indications requiring oral anticoagulation. All enrolled patients underwent a 4-week placebo monitoring period in which INRs were determined on a weekly basis. If the INRs were found to be stable, patients were randomized to receive a 4-week treatment period of either placebo capsules (n = 6), 3 grams of fish oil daily (n = 5), or 6 grams of fish oil daily (n = 5). Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. Five patients were discontinued from the study due to noncompliance (2) and unstable INRs (3). There was no statistically significant difference in INRs between the placebo lead-in and treatment period within each group (P = 0.82). There was also no difference in INRs found between groups (P= 0.41). One bruising episode was reported, yet no major bleeding episodes were observed during the study. Fish oil supplementation in doses of 3-6 grams per day does not seem to create a statistically significant effect on the anticoagulation status of patients receiving chronic warfarin therapy.

Dosimetric analysis of stereotactic body radiation therapy for pancreatic cancer using MR-guided Tri-60Co unit, MR-guided LINAC, and conventional LINAC-based plans.

PubMed

Ramey, Stephen James; Padgett, Kyle R; Lamichhane, Narottam; Neboori, Hanmath J; Kwon, Deukwoo; Mellon, Eric A; Brown, Karen; Duffy, Melissa; Victoria, James; Dogan, Nesrin; Portelance, Lorraine

2018-03-01

This study aims to perform a dosimetric comparison of 2 magnetic resonance (MR)-guided radiation therapy systems capable of performing online adaptive radiation therapy versus a conventional radiation therapy system for pancreas stereotactic body radiation therapy. Ten cases of patients with pancreatic adenocarcinoma previously treated in our institution were used for this analysis. MR-guided tri-cobalt 60 therapy (MR-cobalt) and MR-LINAC plans were generated and compared with conventional LINAC (volumetric modulated arc therapy) plans. The prescription dose was 40 Gy in 5 fractions covering 95% of the planning tumor volume for the 30 plans. The same organs at risk (OARs) dose constraints were used in all plans. Dose-volume-based indices were used to compare PTV coverage and OAR sparing. The conformity index of 40 Gy in 5 fractions covering 95% of the planning tumor volume demonstrated higher conformity in both LINAC-based plans compared with MR-cobalt plans. Although there was no difference in mean conformity index between LINAC and MR-LINAC plans (1.08 in both), there was a large difference between LINAC and MR-cobalt plans (1.08 vs 1.52). Overall, 79%, 72%, and 78% of critical structure dosimetric constraints were met with LINAC, MR-cobalt, and MR-LINAC plans, respectively. The MR-cobalt plans delivered more doses to all OARs compared with the LINAC plans. In contrast, the doses to the OARs of the MR-LINAC plans were similar to LINAC plans except in 2 cases: liver mean dose (MR-LINAC, 2 .8 Gy vs LINAC, 2.1 Gy) and volume of duodenum receiving at least 15 Gy (MR-LINAC, 13.2 mL vs LINAC, 15.4 mL). Both differences are likely not clinically significant. This study demonstrates that dosimetrically similar plans were achieved with conventional LINAC and MR-LINAC, whereas doses to OARs were statistically higher for MR-cobalt compared with conventional LINAC plans because of low-dose spillage. Given the improved tumor-tracking capabilities of MR-LINAC, further studies

Colonic endoscopic mucosal resection in patients taking anticoagulants: Is heparin bridging therapy necessary?

PubMed

Fujita, Minoru; Murao, Takahisa; Osawa, Motoyasu; Hirai, Shinsuke; Fukushima, Shinya; Yo, Syogen; Nakato, Rui; Ishii, Manabu; Matsumoto, Hiroshi; Tamaki, Takahiko; Sakakibara, Takashi; Shiotani, Akiko

2018-05-01

Heparin bridging therapy (HBT) reportedly increases the risk of post-procedural bleeding, and its safety during endoscopic interventions remains unclear. We aimed to evaluate the effects of peri-procedural HBT in patients taking anticoagulants who underwent colonic endoscopic mucosal resection (EMR) for polyps. Patients who underwent colonic EMR while taking a single anticoagulant agent were enrolled in this study. Anticoagulants were temporarily ceased in all patients either without (the non-HBT group, prospectively enrolled) or with HBT (the HBT group, retrospectively enrolled). The incidences of post-procedural bleeding and anemia exacerbation and their length of hospitalization were evaluated and compared. There were altogether 43 consecutive adult patients (30 men; mean age 72.2 ± 7.4 years) in the non-HBT group and 41 sex- and age-matched adults (32 men; mean age 72.9 ± 8.3 years) in the HBT group. There were no significant differences in the location, number or size of resected polyps between the two groups. The percentage of patients with post-procedural bleeding within 2 weeks after colonic EMR in the non-HBT group was lower than that in the HBT group (2.3% vs 9.8%, P = 0.15), although the frequency of anemia exacerbation was not significantly different between the two groups. The total hospitalization length was shorter in the non-HBT compared with the HBT group (4.5 days vs 6.0 days, P < 0.001). No patient in either group developed embolism during hospitalization. Colonic EMR with the temporary cessation of anticoagulants without HBT may be acceptable and beneficial for patients taking anticoagulants. © 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Novel oral anticoagulants for atrial fibrillation.

PubMed

How, Choon How

2015-12-01

Anticoagulation therapy is effective in preventing primary and secondary thromboembolic events due to atrial fibrillation. Warfarin, which was approved by the United States in 1954, was the only long-term oral anticoagulation therapy till the approval of dabigatran in 2010, and of rivaroxaban and other direct factor Xa inhibitors from 2011, forming a group known as novel oral anticoagulants (NOAC). NOAC have fewer food and drug interactions compared to warfarin; hence, the patient will require fewer clinic visits. However, the short half-life of NOAC means that twice-a-day dosing is needed and there is higher risk of a prothrombotic state when doses are missed. Other disadvantages are the lack of long-term data on NOAC, their high cost and the current lack of locally available antidotes.

Novel oral anticoagulants for atrial fibrillation

PubMed Central

How, Choon How

2015-01-01

Anticoagulation therapy is effective in preventing primary and secondary thromboembolic events due to atrial fibrillation. Warfarin, which was approved by the United States in 1954, was the only long-term oral anticoagulation therapy till the approval of dabigatran in 2010, and of rivaroxaban and other direct factor Xa inhibitors from 2011, forming a group known as novel oral anticoagulants (NOAC). NOAC have fewer food and drug interactions compared to warfarin; hence, the patient will require fewer clinic visits. However, the short half-life of NOAC means that twice-a-day dosing is needed and there is higher risk of a prothrombotic state when doses are missed. Other disadvantages are the lack of long-term data on NOAC, their high cost and the current lack of locally available antidotes. PMID:26702159

An international survey of current practice in the laboratory assessment of anticoagulant therapy with heparin.

PubMed

Favaloro, Emmanuel J; Bonar, Roslyn; Sioufi, John; Wheeler, Michael; Low, Joyce; Aboud, Margaret; Lloyd, John; Street, Alison; Marsden, Katherine

2005-06-01

We conducted a survey of laboratory practice for assessment of heparin anticoagulant therapy by participants of the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP). A questionnaire was sent to 646 laboratories enrolled in the Haematology component of the QAP, requesting details of tests used for monitoring heparin therapy. Seventy laboratories (10.8%) returned results that indicated that they performed laboratory monitoring of heparin therapy. Most laboratories (69/70 = 98.6%) use the activated partial thromboplastin time (APTT) to monitor unfractionated heparin, with eight (11.4%) also using the APTT for monitoring low molecular weight (LMW) heparin. Five (7.1%) laboratories use the thrombin time (TT) test to help monitor heparin therapy and 37 (52.9%) laboratories use an anti-Xa assay to monitor heparin (either LMW or unfractionated). Normal reference ranges (NRR) for APTT differed considerably between laboratories, even those using the same reagent. Therapeutic ranges (TR) also differed considerably between laboratories, for both APTT and the anti-Xa assay. Laboratory differences in NRR and TR using the same reagents could only be partly explained by the use of different instrumentation. There is a large variation in current laboratory practice relating to monitoring of heparin anticoagulant therapy. This finding is similar to that of a similar survey conducted by the RCPA QAP almost a decade ago. This study suggests that better standardisation is still required for laboratory monitoring of heparin therapy.

Optimal Anticoagulant Therapy in ST Elevation Myocardial Infarction Interventions.

PubMed

Oliveros, Estefania; Mehta, Sameer; Flores, Ana Isabel; Pena, Camilo; Cohen, Salomon; Kostela, Jennifer C; Rowen, Rebecca; Treto, Kevin

2012-10-01

Bivalirudin is a direct thrombin inhibitor. It is a new recommendation for the treatment of patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention. Bivalirudin combined with aspirin and P2Y 12 inhibitors has proved to be an effective and safe choice for the management of thrombus in coronary artery disease. The use of bivalirudin compared with the combination of heparin plus glycoprotein IIb/IIIa inhibitors as anticoagulant therapy is associated with reduced severe bleeding and inpatient mortality, as well as diminished costs. There is only a slight increase of late stent thrombosis, which may be controlled with the use of thienopyridines. Copyright © 2012 Elsevier Inc. All rights reserved.

Antiplatelet and anticoagulation therapy during percutaneous coronary interventions: A review for the interventionalist.

PubMed

Basman, Craig; Tariq, Afnan; Parmar, Yuvrajsinh J; Asti, Deepak; Coplan, Neil L; Singh, Varinder P; Reimers, Carl D

2018-06-19

Pharmacotherapy for percutaneous coronary interventions is essential to optimize the balance between thrombosis and bleeding. Currently, choices abound for the selection of antiplatelet and anticoagulation therapies during percutaneous intervention (PCI). This review article discusses the mechanisms, pharmacokinetics/dynamics, and clinical data behind the various pharmacotherapies including; aspirin, thienopyridines, glycoprotein IIb/IIIa inhibitors, vorapaxar, heparin, direct thrombin inhibitors, and factor Xa inhibitors. © 2018, Wiley Periodicals, Inc.

Athletes and blood clots: individualized, intermittent anticoagulation management.

PubMed

Berkowitz, J N; Moll, S

2017-06-01

Essentials Athletes on anticoagulants are typically prohibited from participation in contact sports. Short-acting anticoagulants allow for reconsideration of this precedent. An individualized pharmacokinetic/pharmacodynamics study can aid patient-specific management. Many challenges and unresolved issues exist regarding such tailored intermittent dosing. Athletes with venous thromboembolism (VTE) are typically prohibited from participating in contact sports during anticoagulation therapy, but such mandatory removal from competition can cause psychological and financial detriments for athletes and overlooks patient autonomy. The precedent of compulsory removal developed when options for anticoagulation therapy were more limited, but medical advances now allow for rethinking of the management of athletes with VTE. We propose a novel therapeutic approach to the treatment of athletes who participate in contact sports and require anticoagulation. A personalized pharmacokinetic/pharmacodynamics study of a direct oral anticoagulant can be performed for an athlete, which can inform the timing of medication dosing. Managed carefully, this can allow athletic participation when plasma drug concentration is minimal (minimizing bleeding risk) and prompt resumption of treatment after the risk of bleeding sufficiently normalizes (maximizing therapeutic time). © 2017 International Society on Thrombosis and Haemostasis.

Standards of care issues with anticoagulation in real-world populations.

PubMed

2015-01-01

Current guidelines recommend anticoagulants for reducing the risk of stroke in appropriate patients with nonvalvular atrial fibrillation (NVAF) and for the acute treatment of venous thromboembolism (VTE) and the prevention of recurrent VTE. Warfarin is the standard of care for both NVAF and VTE, yet International Normalized Ratio (INR) control remains suboptimal, even in the clinical trial setting. Maintaining INR within the recommended therapeutic range is associated with better outcomes in these distinct populations. In VTE, high rates of recurrence have been reported during the first few weeks of treatment, emphasizing the importance of surveillance during this time and of early optimization of anticoagulation therapy. The NVAF population tends to have more comorbidities and requires longer-term therapy. It is important to keep in mind that real-world patient populations are more complex than those in controlled studies. Patients with multiple comorbidities are particularly challenging, and physicians may focus on clinically urgent issues rather than anticoagulation optimization. Despite the many complexities associated with the use of warfarin, it remains a mainstay of anticoagulation therapy. Aligning financial incentives and improving care coordination are important factors in moving toward better outcomes for patients who need anticoagulation therapy. The increased focus on value-based care and evolving approaches to patient treatment could lead more physicians and payers to consider alternatives to warfarin, including the use of novel oral anticoagulants.

Using Artificial Intelligence to Reduce the Risk of Nonadherence in Patients on Anticoagulation Therapy

PubMed Central

Labovitz, Daniel L.; Shafner, Laura; Gil, Morayma Reyes; Virmani, Deepti; Hanina, Adam

2017-01-01

Background and Purpose This study evaluated the use of an artificial intelligence (AI) platform on mobile devices in measuring and increasing medication adherence in stroke patients on anticoagulation therapy. The introduction of direct oral anticoagulants (DOACs), while reducing the need for monitoring, have also placed pressure on patients to self-manage. Suboptimal adherence goes undetected as routine laboratory tests are not reliable indicators of adherence, placing patients at increased risk of stroke and bleeding. Methods A randomized, parallel-group, 12-week study was conducted in adults (n = 28) with recently diagnosed ischemic stroke receiving any anticoagulation. Patients were randomized to daily monitoring by the AI Platform (intervention) or to no daily monitoring (control). The AI application visually identified the patient, the medication and confirmed ingestion. Adherence was measured by pill counts and plasma sampling in both groups. Results For all patients (n = 28), mean (standard deviation [SD]) age was 57 (13.2) years and 53.6% were female. Mean (SD) cumulative adherence based on the AI Platform was 90.5% (7.5%). Plasma drug concentration levels indicated that adherence was 100% (15 of 15) and 50% (6 of 12) in the intervention and control groups, respectively. Conclusions Patients, some with little experience using a smartphone, successfully used the technology and demonstrated a 50% improvement in adherence based on plasma drug concentration levels. For patients receiving DOACs, absolute improvement increased to 67%. Real-time monitoring has the potential to increase adherence and change behavior, particularly in patients on DOAC therapy. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02599259. PMID:28386037

Sustained impact of anticoagulant control achieved in an anticoagulation management service after transfer of management to the primary care physician.

PubMed

Bungard, Tammy J; Ritchie, Bruce; Garg, Sipi; Tsuyuki, Ross T

2012-02-01

To determine whether the impact of anticoagulant control achieved in an Anticoagulation Management Service (AMS) is sustained after transfer of anticoagulation management to the primary care physician (PCP), and to assess patient satisfaction with their anticoagulation management by both the AMS and PCP. Prospective, randomized trial. Pharmacist-directed ambulatory AMS located in a tertiary medical care facility and PCP practices in Canada. Sixty-two adults who had received at least 6 months of warfarin therapy managed by the AMS. Patients were randomly assigned to remain with AMS care (32 patients) or to transfer their anticoagulation management care to their PCP (30 patients). After 4.5 months of care, patients in both groups completed a validated survey instrument assessing their satisfaction with the management of their warfarin therapy. Of 295 patients screened, most were excluded from the study for denying consent or for having previous bleeding or clotting complications while taking warfarin. Patients in the AMS and PCP groups who completed the study were similar in age (median 70 and 76 yrs, respectively), and most had atrial fibrillation as an indication for warfarin (75% and 83%, respectively). The primary outcome measure-mean percentage of time within the desired international normalized ratio (INR) range after 6 months-was compared between the two groups, using both the actual range (INR 2.5 ± 0.5) and an expanded range (INR 2.5 ± 0.7). No significant difference was noted in this outcome between the groups (73.5 ± 19.1% vs 76.9 ± 24.5% for the AMS vs PCP groups, p=0.54). Other outcome measures were rates of thrombotic and hemorrhagic events resulting in emergency department visits or hospitalizations, patients' overall satisfaction with warfarin therapy, and patients' preferred anticoagulation management strategy. Two hemorrhagic events and one thrombotic event occurred in each group. Patients were more satisfied with their anticoagulant

[Secondary osteoporosis induced by anticoagulants?].

PubMed

Riess, H; Loew, A; Himmelreich, G

2001-07-01

Generalized osteoporosis is a result of different causes and pathogenic mechanisms, which often combine forces to become clinically relevant. Among the different exogenic factors, drugs play an important role, frequently in connection with other factors such as immobilization or pregnancy. It has been suggested that anticoagulation therapy with heparins or coumarins may induce osteoporotic changes or enhance the development of osteoporosis for other reasons. According to in vitro experiments, preclinical trials, and clinical investigations, it seems reasonable to assume that heparins induce increased bone loss in a time- and dose-related manner. Low-molecular-weight heparins most likely have less effect on bone turnover when compared to unfractionated heparin. Oral anticoagulation therapy with vitamin K-antagonists is believed to have a weak effect on induction of osteoporosis, but clinical studies are contradictory. In spite of the fact that a relevant effect of these drugs on the induction of osteoporosis is questionable, it must be taken into consideration that anticoagulant drugs may enhance the negative effects on bone density of other risk factors capable of inducing osteoporosis such as immobilization, pregnancy, or endocrinological disorders.

Risk of gastrointestinal bleeding during anticoagulant treatment.

PubMed

Lanas-Gimeno, Aitor; Lanas, Angel

2017-06-01

Gastrointestinal bleeding (GIB) is a major problem in patients on oral anticoagulation therapy. This issue has become even more pressing since the introduction of direct oral anticoagulants (DOACs) in 2009. Areas covered: Here we review current evidence related to GIB associated with oral anticoagulants, focusing on randomized controlled trials, meta-analyses, and post-marketing observational studies. Dabigatran 150 mg twice daily and rivaroxaban 20 mg once daily increase the risk of GIB compared to warfarin. The risk increase with edoxaban is dose-dependent, while apixaban shows apparently, no increased risk. We summarize what is known about GIB risk factors for individual anticoagulants, the location of GIB in patients taking these compounds, and prevention strategies that lower the risk of GIB. Expert opinion: Recently there has been an important shift in the clinical presentation of GIB. Specifically, upper GIB has decreased with the decreased incidence of peptic ulcers due to the broad use of proton pump inhibitors and the decreased prevalence of H. pylori infections. In contrast, the incidence of lower GIB has increased, due in part to colonic diverticular bleeding and angiodysplasia in the elderly. In this population, the addition of oral anticoagulation therapy, especially DOACs, seems to increase the risk of lower GIB.

Pathology consultation on anticoagulation monitoring: factor X-related assays.

PubMed

Wool, Geoffrey D; Lu, Chuanyi M

2013-11-01

To review various anticoagulation therapies and related laboratory monitoring issues, with a focus on factor X-related chromogenic assays. A case-based approach is used to review pertinent published literatures and product inserts of anticoagulation drugs and to look back on clinical use of factor X-related chromogenic assays. The number of anticoagulants available to clinicians has increased greatly in the past decade. Whether and how these anticoagulants should be monitored are areas of uncertainty for clinicians, which can lead to misuse of laboratory assays and suboptimal patient management. Factor X-related assays are of particular concern because of the similar and often confusing test names. Based on a common clinical case scenario and literature review regarding anticoagulant monitoring, an up-to-date discussion and review of the various factor X-related assays are provided, focusing on the differences in test designs and clinical utilities between the chromogenic anti-Xa and chromogenic factor X activity assays. Anticoagulation therapy and related laboratory monitoring are rapidly evolving areas of clinical practices. A good knowledge of relevant laboratory assays and their clinical applications is necessary to help optimize patient care.

Utilization of Anticoagulation Therapy in Medicare Patients with Nonvalvular Atrial Fibrillation

PubMed Central

Fitch, Kate; Broulette, Jonah; Pyenson, Bruce; Iwasaki, Kosuke; Kwong, Winghan Jacqueline

2012-01-01

Background Clinical guidelines recommend oral anticoagulation for stroke prevention in patients with atrial fibrillation (AF) at moderate or high risk for stroke but not at high risk for bleeding; however, studies consistently report suboptimal use of such therapy. This study used Medicare Part D claims data to assess the use of warfarin in the Medicare population. Objectives To compare real-world warfarin utilization with current treatment guideline recommendations, and to assess the effect of warfarin exposure level on patient outcomes in Medicare beneficiaries with nonvalvular AF (NVAF). Methods Patients who were recently diagnosed with NVAF were identified using a random 5% sample of Research Identifiable Files of Medicare beneficiaries in 2006 or 2007. Individuals with moderate-to-high stroke risk per CHADS2 but not at high bleeding risk per ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score were evaluated for warfarin use, as identified by the presence of ≥1 warfarin prescription claims within 12 months after the index diagnosis. Warfarin exposure level was assessed by the proportion of days covered during the 12-month follow-up period. The effect of warfarin exposure on ischemic stroke and major bleeding event rates during the 12-month follow-up period were assessed using multivariate logistic regression. Results Data from 14,149 newly diagnosed patients with NVAF (mean age, 79 years; 58.7% female) were analyzed, and of these, 7524 (53.2%) patients were identified as having moderate-to-high stroke risk and not being at high bleeding risk. Of these patients, 3110 (41.3%) did not receive warfarin within 12 months of the index diagnosis. The risk for ischemic stroke was significantly lower in those with warfarin exposure versus no warfarin exposure (adjusted odds ratio [OR], 0.51; confidence interval [CI], 0.43–0.61; P <.001) and in patients with warfarin proportion of days covered ≥80% versus those with proportion of days

Clinical effectiveness and cost-effectiveness of different models of managing long-term oral anticoagulation therapy: a systematic review and economic modelling.

PubMed

Connock, M; Stevens, C; Fry-Smith, A; Jowett, S; Fitzmaurice, D; Moore, D; Song, F

2007-10-01

To examine the clinical effectiveness and cost-effectiveness of self-testing and self-management of oral anticoagulation treatment compared with clinic-based monitoring. Major electronic databases were searched up to September 2005. A systematic review was undertaken of relevant data from selected studies. Results about complication events and deaths were pooled in meta-analyses using risk difference (RD) as the outcome statistic. Heterogeneity across trials and possible publication bias were statistically measured. Subgroup analyses (post hoc) were conducted to compare results of self-testing versus self-management, low versus high trial quality, trials conducted in the UK versus trials in other countries and industry versus other sponsors. A Markov-type, state-transition model was developed. Stochastic simulations using the model were conducted to investigate uncertainty in estimated model parameters. In the 16 randomised and eight non-randomised trials selected, patient self-monitoring of oral anticoagulation therapy was found to be more effective than poor-quality usual care provided by family doctors and as effective as good-quality specialised anticoagulation clinics in maintaining the quality of anticoagulation therapy. There was no significant RD of major bleeding events between patient self-monitoring and usual care controls and pooled analyses found that compared with primary care or anticoagulation control (AC) clinics, self-monitoring was statistically significantly associated with fewer thromboembolic events. However, the reduction in complication events and deaths was not consistently associated with the improvement of AC; in some trials this may be due to alternative explanations, including patient education and patient empowerment. Also, the improved AC and the reduction of major complications and deaths by patient self-monitoring were mainly observed in trials conducted outside the UK. According to UK-specific data, for every 100 eligible patients

Monitoring anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome.

PubMed

Isert, Mecki; Miesbach, Wolfgang; Schüttfort, Gundolf; Weil, Yvonne; Tirneci, Vanessa; Kasper, Alexander; Weber, Adele; Lindhoff-Last, Edelgard; Herrmann, Eva; Linnemann, Birgit

2015-08-01

Because of the possible interference of antiphospholipid antibodies (APL) with the phospholipid component of thromboplastin reagents, concerns have been raised about the validity of international normalized ratio (INR) testing to monitor anticoagulant therapy with vitamin K antagonists in patients with antiphospholipid syndrome (APS). To investigate the reliability of the INR, we determined the INR using various prothrombin time (PT) assays and compared the results with those of a chromogenic factor X (CFX) assay. The study cohort consisted of 40 APS patients and 100 APL-negative patients who were on anticoagulant therapy for reasons other than APS. The agreement (i.e. the percentage of patients with a difference ≤0.5 INR units) between the PT-derived INR and CFX-derived INR equivalents was only moderate in both patient groups. The best agreement with CFX-derived INR equivalents was observed for the Thromborel S reagent in APS patients (69.1 %) and for Neoplastin Plus in APL-negative patients (72.0 %). Regarding the results for the point-of-care system CoaguChek XS, an agreement between the INR and the CFX-derived INR equivalent was less frequently observed in the APS patients (55.6 vs. 67.8 %; p = 0.050). When considering all 3058 pairs of INR tests within the international sensitivity index (ISI)-calibrated range of 1.5 to 4.5 s, we did not observe a higher variability of INR values in either the APS patient group or the subgroup of APS patients positive for lupus coagulants compared with the APL-negative controls. In conclusion, monitoring vitamin K antagonists (VKA) therapy with laboratory INR measurements seems to be suitable for the majority of APS patients.

Practical management of anticoagulation in patients with atrial fibrillation.

PubMed

Kovacs, Richard J; Flaker, Greg C; Saxonhouse, Sherry J; Doherty, John U; Birtcher, Kim K; Cuker, Adam; Davidson, Bruce L; Giugliano, Robert P; Granger, Christopher B; Jaffer, Amir K; Mehta, Bella H; Nutescu, Edith; Williams, Kim A

2015-04-07

Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy, and the interactions of those patients in the matrix of care. The management of anticoagulation has become a "team sport" involving multiple specialties in multiple sites of care. The American College of Cardiology, through the College's Anticoagulation Initiative, convened a roundtable of experts from multiple specialties to discuss topics important to the management of patients requiring anticoagulation and to make expert recommendations on issues such as the initiation and interruption of anticoagulation, quality of anticoagulation care, management of major and minor bleeding, and treatment of special populations. The attendees continued to work toward consensus on these topics, and present the key findings of this roundtable in a state-of- the-art review focusing on the practical aspects of anticoagulation care for the patient with atrial fibrillation. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

INR goal attainment and oral anticoagulation knowledge of patients enrolled in an anticoagulation clinic in a Veterans Affairs medical center.

PubMed

Baker, Jennifer W; Pierce, Kristi L; Ryals, Casey A

2011-03-01

In January 2009, the Joint Commission implemented a National Patient Safety Goal (NPSG) for ambulatory care, NPSG 3E, intended to reduce harm associated with the use of anticoagulation therapy. The 2011 NPSG 3E encompasses 8 elements of performance, including requirements that each organization (a) provide education regarding anticoagulation therapy to staff, patients, and families and (b) evaluate its safety practices and take appropriate action to improve its practices. The Alvin C. York (ACY) outpatient anticoagulation clinic provides education to new patients and their families at the initial clinic visit, with follow-up reinforcement of education as needed throughout their care. To (a) assess the knowledge level of patients receiving warfarin therapy in an anticoagulation clinic using the validated Anticoagulation Knowledge Assessment (AKA) questionnaire and (b) examine the relationship between patient anticoagulation knowledge and anticoagulation control as measured by the international normalized ratio (INR). All ACY Veterans Affairs (VA) anticoagulation clinic patients seen during their routine visit within an 8-week recruitment period from February 2010 to April 2010 were asked to complete the AKA questionnaire. Upon voluntary consent, the questionnaire was completed by the patient either during the clinic visit or returned later by mail. Demographic and clinical data were manually extracted from the computerized patient record system and included age, gender, indication for and duration of anticoagulation therapy, goal INR range, and the 10 INR values preceding the date of consent. A passing score was defined as at least 21 correct responses on the 29-item AKA questionnaire (72.4% correct). Statistical analyses included comparisons of demographic and clinical characteristics for patients with passing versus failing scores, assessed with Pearson chi-square and Fisher's exact test, and bivariate analyses of INR control with anticoagulation knowledge

Regional citrate anticoagulation for continuous renal replacement therapy in severe burns-a retrospective analysis of a protocol-guided approach.

PubMed

Gille, Jochen; Sablotzki, Armin; Malcharek, Michael; Raff, Thomas; Mogk, Martin; Parentin, Torsten

2014-12-01

For critically ill patients, the use of regional citrate anticoagulation as part of continuous renal replacement therapy (CRRT) has become increasingly common in recent years. However, there are scarce data on the use of this technique in patients with burns. The aim of this study was to examine the effectiveness, feasibility and complications of regional citrate anticoagulation for CRRT in burn patients, as well as the effects on coagulation and the electrolyte and acid-base balance. This retrospective study included all patients who received renal replacement therapy with citrate anticoagulation to treat acute kidney injury (AKI) between January 1, 2004 and December 31, 2009 at the burn unit of St. Georg Hospital GmbH in Leipzig. During the examination period, 18 patients were treated using CRRT with regional citrate anticoagulation (CVVHDF in the pre-dilution mode). The median patient age was 64 years (49.5; 71), with a median TBSA of 42.5% (33.25; 52.5) and a median ABSI score of 10 (9; 10). The CRRT was initiated on a median of 6 days (4; 8.75) after admission to the hospital and continued for a median duration of 7 days (5; 8). The median dialysis dose was 38.2mlkgBW(-1)h(-1) (31.8; 42.1). The median effective filter operation time was 67h (46; 72). No relevant disorders associated with acid-base balance, electrolytes or coagulation occurred, and there were no bleeding complications. In terms of bleeding risk and electrolyte and acid-base balance, regional citrate anticoagulation may be considered to be an effective, safe and user-friendly procedure for patients with severe burns and AKI. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Adherence to Guidelines for Oral Anticoagulation after Venous Thrombosis and Pulmonary Embolism

PubMed Central

Ganz, David A; Glynn, Robert J; Mogun, Helen; Knight, Eric L; Bohn, Rhonda L; Avorn, Jerry

2000-01-01

OBJECTIVE Guidelines for oral anticoagulation after deep venous thrombosis (DVT) or pulmonary embolism (PE) have recommended that patients be anticoagulated for at least 3 months after hospital discharge. We sought to determine whether this recommendation was being followed and what patient characteristics predict a shorter than recommended duration of therapy. DESIGN Retrospective cohort study using linked health care claims data. SETTING Routine clinical practice. PATIENTS Five hundred seventy-three members of New Jersey's Medicaid or Pharmacy Assistance for the Aged and Disabled programs aged 65 years and older who were hospitalized for DVT or PE between January 1, 1991 and June 30, 1994. RESULTS Of the 573 patients, 129 (23%) filled prescriptions covering less than 90 days of oral anticoagulant therapy. In multivariate models, African-American race was associated with an increased risk of a shorter than recommended duration of therapy (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.14 to 3.08), but age and gender were not. Patients who used anticoagulants in the year prior to admission were less likely to have a short duration of therapy (OR, 0.30; 95% CI, 0.12 to 0.78), than were patients with PE (OR, 0.58; 95% CI, 0.38 to 0.88). CONCLUSIONS Nearly a quarter of those anticoagulated following DVT or PE received therapy for less than the recommended length of time after hospital discharge, with African Americans more likely to have a shorter than recommended course of treatment. Further research is needed to evaluate the causes of shorter than recommended duration of therapy and racial disparities in anticoagulant use. PMID:11119169

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism - still a challenging issue.

PubMed

Elmi, Giovanna; Di Pasquale, Giuseppe; Pesavento, Raffaele

2017-03-01

As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

Anticoagulation Quality Assessment in Patients with Nonvalvular Atrial Fibrillation (NVAF) and Comparison with Major Trials of Direct-Acting Oral Anticoagulants

DTIC Science & Technology

2016-04-22

Purpose: The benefits of warfarin anticoagulation therapy are strongly correlated with the ability to maintain patients’ INR goal, known as the time...Rosendaal). Differences in TTR calculations could alter perceptions about the effectiveness of warfarin therapy.

Intracerebral Hemorrhages in Adults with Community Associated Bacterial Meningitis in Adults: Should We Reconsider Anticoagulant Therapy?

PubMed Central

Mook-Kanamori, Barry B.; Fritz, Daan; Brouwer, Matthijs C.; van der Ende, Arie; van de Beek, Diederik

2012-01-01

Objective To study the incidence, clinical presentation and outcome of intracranial hemorrhagic complications in adult patients with community associated bacterial meningitis. Methods Nationwide prospective cohort study from all hospitals in the Netherlands, from 1 March 2006, through 31 December 2010. Results Of the 860 episodes of bacterial meningitis that were included, 24 were diagnosed with intracranial hemorrhagic complications: 8 upon presentation and 16 during clinical course. Clinical presentation between patients with or without intracranial hemorrhage was similar. Causative bacteria were Streptococcus pneumoniae in 16 patients (67%), Staphylococcus aureus in 5 (21%), Pseudomonas aeruginosa and Listeria monocytogenes both in 1 patient (4%). Occurrence of intracranial hemorrhage was associated with death (63% vs. 15%, P<0.001) and unfavorable outcome (94% vs. 34%, P<0.001). The use of anticoagulants on admission was associated with a higher incidence of intracranial hemorrhages (odds ratio 5.84, 95% confidence interval 2.17–15.76). Conclusion Intracranial hemorrhage is a rare but devastating complication in patients with community-associated bacterial meningitis. Since anticoagulant therapy use is associated with increased risk for intracranial hemorrhage, physicians may consider reversing or temporarily discontinuing anticoagulation in patients with bacterial meningitis. PMID:23028898

Development of Interstitial Lung Disease after Initiation of Apixaban Anticoagulation Therapy.

PubMed

Tomari, Shinya; Homma, Kazunari; Noguchi, Teruo; Aiba, Takeshi; Matsuki, Takayuki; Suzuki, Rieko; Koga, Masatoshi; Takigami, Masao; Tagawa, Hiroshi; Hashimoto, Taisuke; Toyoda, Kazunori

2016-07-01

Nonvitamin K antagonist oral anticoagulants may cause interstitial lung disease (ILD) similar to that seen for other cardiovascular drugs. The aim of this study was to determine trends and medical conditions associated with ILD in patients taking apixaban. A single-center observational survey conducted between February 2013 and May 2015 examined patients who developed ILD after initiation of apixaban administration. Chest computed tomography showed that 4 (~.45%) out of approximately 870 apixaban users developed ILD. All patients were elderly Japanese men with decreased creatinine clearance who had nonvalvular atrial fibrillation. Three of the four were confirmed smokers, whereas three had a history of lung disease. Dyspnea occurred during the initial week after starting apixaban administration in 3 patients and at 90 days in 1 patient. All patients underwent methylprednisolone pulse therapy, with three requiring mechanical ventilation. Although 2 patients recovered, the other two died of respiratory failure. Development of ILD during anticoagulation with apixaban is not rare. When apixaban is administered in elderly high-risk patients, subjects need to be carefully monitored for respiratory symptoms. As drug-induced ILD is often reported in Japan, further studies that clarify if these types of cases are common in countries other than Japan will also need to be undertaken. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Clinical Outcome of a Portosplenomesenteric Venous Thrombosis in Necrotizing Acute Pancreatitis with Protein C and S Deficiency Treated by Anticoagulation Therapy Alone.

PubMed

Ankouane, Firmin; Kowo, Mathurin; Ngo Nonga, Bernadette; Magny, Eric; Hell Medjo, Edith; Ndjitoyap Ndam, Elie Claude

2015-01-01

Cases of splanchnic venous thrombosis have not been described in Cameroon. Their prevalence in acute pancreatitis is variable. With the emergence of acute intra-abdominal infections including typhoid fever and peritoneal tuberculosis in situations of acquired immunodeficiency syndrome, these cases will become frequent. We report the case of a portosplenomesenteric venous thrombosis related to necrotizing acute pancreatitis associated with proteins C and S deficiency, in a 46-year-old Cameroonian man, without particular past medical history. He was admitted for abdominal pain which had been evolving for 3 weeks and accompanied by vomiting. In the absence of hemorrhagic risk factor, the patient received low molecular weight heparin followed by oral warfarin. The abdominal ultrasound check on the 12th day showed a partial recanalization of venous thrombosis. The abdominal contrast-enhanced CT scanner at day 30 on oral anticoagulation therapy showed collateral vessels and small bowel edema. At the same time the upper gastrointestinal endoscopy showed grade II esophageal varices. We have maintained oral anticoagulation therapy. This case highlights that an early effective anticoagulation heparin therapy is needed for a clear benefit in case of suspected PSMVT. It is certain that the sooner the treatment is given, the better outcome will be.

Anticoagulation knowledge in patients with atrial fibrillation: An Australian survey.

PubMed

Obamiro, Kehinde O; Chalmers, Leanne; Lee, Kenneth; Bereznicki, Bonnie J; Bereznicki, Luke R E

2018-03-01

Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia in clinical practice, and is associated with a significant medical and economic burden. Anticoagulants reduce the risk of stroke and systemic embolism by approximately two-thirds compared with no therapy. Knowledge regarding anticoagulant therapy can influence treatment outcomes in patients with AF. To measure the level of anticoagulation knowledge in patients with AF taking oral anticoagulants (OACs), investigate the association between patient-related factors and anticoagulation knowledge, and compare these results in patients taking warfarin and direct-acting oral anticoagulant (DOACs). Participants were recruited for an online survey via Facebook. Survey components included the Anticoagulation Knowledge Tool, the Perception of Anticoagulant Treatment Questionnaires (assessing treatment expectations, convenience and satisfaction), a modified Cancer Information Overload scale and the Morisky Medication Adherence Scale. Treatment groups were compared and predictors of OAC knowledge were identified. Participants taking warfarin had a higher knowledge score compared with those taking DOACs (n = 386, 73% ± 13% vs 66% ± 14%, P<.001). Advancing age, type of OAC, health information overload and ease of OAC use (treatment expectation) were significant predictors of knowledge. Treatment expectation, including the belief that OAC treatment would cause bleeding side effects, varied significantly between participants taking warfarin and DOACs (P = .011). The study identified knowledge gaps in patients taking OACs, and these deficiencies appeared to be greater in participants taking DOACs. Knowledge assessment should be integrated into patient counselling sessions to help identify and resolve knowledge deficits. © 2018 John Wiley & Sons Ltd.

Oral anticoagulation management in patients with atrial fibrillation undergoing cardiac implantable electronic device implantation.

PubMed

Black-Maier, Eric; Kim, Sunghee; Steinberg, Benjamin A; Fonarow, Gregg C; Freeman, James V; Kowey, Peter R; Ansell, Jack; Gersh, Bernard J; Mahaffey, Kenneth W; Naccarelli, Gerald; Hylek, Elaine M; Go, Alan S; Peterson, Eric D; Piccini, Jonathan P

2017-09-01

Oral anticoagulation (OAC) therapy is associated with increased periprocedural risks after cardiac implantable electronic device (CIED) implantation. Patterns of anticoagulation management involving non-vitamin K antagonist oral anticoagulants (NOACs) have not been characterized. Anticoagulation strategies and outcomes differ by anticoagulant type in patients undergoing CIED implantation. Using the nationwide Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we assessed how atrial fibrillation (AF) patients undergoing CIED implantation were cared for and their subsequent outcomes. Outcomes were compared by oral anticoagulant therapy (none, warfarin, or NOAC) as well as by anticoagulation interruption status. Among 9129 AF patients, 416 (5%) underwent CIED implantation during a median follow-up of 30 months (interquartile range, 24-36). Of these, 60 (14%) had implantation on a NOAC. Relative to warfarin therapy, those on a NOAC were younger (70.5 years [range, 65-77.5 years] vs 77 years [range, 70-82 years]), had less valvular heart disease (15.0% vs 31.3%), higher creatinine clearance (67.3 [range, 59.7-99.0] vs 65.8 [range, 50.0-91.6]), were more likely to have persistent AF (26.7% vs 22.9%), and use concomitant aspirin (51.7% vs 35.2%). OAC therapy was commonly interrupted for CIED in 64% (n = 183 of 284) of warfarin patients and 65% (n = 39 of 60) of NOAC patients. Many interrupted patients received intravenous bridging anticoagulation: 33/183 (18%) interrupted warfarin and 4/39 (10%) interrupted NOAC patients. Thirty-day periprocedure bleeding and stroke adverse events were infrequent. Management of anticoagulation among AF patients undergoing CIED implantation is highly variable, with OAC being interrupted in more than half of both warfarin- and NOAC-treated patients. Bleeding and stroke events were infrequent in both warfarin and NOAC-treated patients. © 2017 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.

Scintigraphic detection of occult hemorrhage in a patient receiving anticoagulants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenbaum, R.C.; Johnston, G.S.; Whitley, N.O.

1986-02-01

The exact location of hemorrhage complicating anticoagulant therapy is sometimes difficult to establish. We present a case in which imaging with 99mTc-labeled red cells had a significant role in the diagnosis of soft-tissue bleeding in a paraplegic patient receiving long-term anticoagulation.

Satisfaction with oral anticoagulants in patients with atrial fibrillation

PubMed Central

Suárez Fernández, Carmen; Castilla-Guerra, Luis; Cantero Hinojosa, Jesus; Suriñach, Josep Maria; Acosta de Bilbao, Fernando; Tamarit, Juan José; Diaz Diaz, José Luis; Hernandez, Jose Luis; Pose, Antonio; Montero-Pérez-Barquero, Manuel; Roquer, Jaume; Gállego, Jaime; Vivancos, José; Mostaza, Jose María

2018-01-01

Background Although, by itself, atrial fibrillation is associated with an impairment of quality of life antithrombotic therapy may play a role. Objective To evaluate the satisfaction with anticoagulant treatment in patients with nonvalvular atrial fibrillation who attended internal medicine departments in Spain. Methods Patients from two different cross-sectional studies were combined. To measure the satisfaction with anticoagulant treatment, the Anti-Clot-Treatment Scale (ACTS) questionnaire was completed by every patient. A multivariate analysis was performed to determine the variables associated with satisfaction of patients receiving oral anticoagulants. Results A total of 1,309 patients (mean age 78.5±8.4 years; 49.3% men; CHA2DS2VASC 4.9±1.5; HAS-BLED 2.0±0.9) were included in the study, of whom 902 (68.9%) were taking vitamin K antagonists (VKA) and 407 (31.1%) direct oral anticoagulants (DOACs). Overall, satisfaction with oral anticoagulation was high (ACTS Burdens scale 49.69±9.45; ACTS Benefits scale 11.35±2.61). The perceived burdens with anticoagulant treatment were lower in men, as well as in patients with no dependency, normal renal function, who were not polymedicated, or who had moderate bleeding risk. Among patients taking VKA, those subjects with a lower number of International Normalized Ratio (INR) determinations in the last 6 months or with an optimal time in the therapeutic range exhibited a lower perceived burden. Patients taking DOACs (vs VKA) showed a lower perceived burden with anticoagulation. Benefits with anti-coagulation were higher in men, younger patients, those with no dependency, or low bleeding risk. Perceived benefits were higher in patients taking DOACs (vs VKA). Conclusion Satisfaction with oral anticoagulation was high in patients with nonvalvular atrial fibrillation, who were attending internal medicine departments daily in Spain. Among patients taking VKA, those subjects with a lower number of INR determinations in the

Optical profiling of anticoagulation status (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tshikudi, Diane M.; Tripathi, Markandey M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.

2016-02-01

Defective blood coagulation resulting from excessive procoagulant activity often leads to thrombotic disorders such as stroke and myocardial infarction. A variety of oral and injectable anticoagulant drugs are prescribed to prevent or treat life-threatening thrombosis. However, due to bleeding complications often associated with anticoagulant treatment, routine monitoring and accurate dosing of anticoagulant therapy is imperative. We have developed Optical thromboelastography (OTEG), a non-contact approach that utilizes a drop of whole blood to measure blood coagulation status in patients. Here, we demonstrate the capability of OTEG for rapidly monitoring anticoagulation in whole blood samples. OTEG monitors coagulation status by assessing changes in blood viscosity from temporal intensity fluctuations of laser speckle patterns during clotting. In OTEG a blood drop is illuminated with coherent light and the blood viscosity is measured from the speckle intensity autocorrelation curve, g2 (t). The metrics, clotting time (R+k), clot progression (angle) and maximum clot stiffness (MA) are then extracted. The aim of the current study was to evaluate the accuracy of OTEG in assessing anticoagulation status of common anticoagulants including heparin, argatroban and rivaroxaban status. A dose-dependent prolongation of R+k was observed in anticoagulated blood, which closely corresponded with standard-reference Thromboelastography (TEG) (r 0.87-0.99, P>0.01 for all cases). OTEG angle was unaltered by anticoagulation whereas TEG angle presented a dose-dependent diminution probably linked to clot rupture. In both OTEG and TEG, MA was unaffected by heparin, argatroban or rivaroxaban. We conclude that OTEG can accurately monitor anticoagulation status following treatment, potentially providing a powerful tool for routine monitoring of patients in the doctor's office or in the home setting.

[Factors influencing activity of oral anticoagulants. Interactions with drugs and food].

PubMed

Sawicka-Powierza, Jolanta; Rogowska-Szadkowska, Dorota; Ołtarzewska, Alicja Małgorzata; Chlabicz, Sławomir

2008-05-01

Oral anticoagulants (OAC) are commonly used as a life-long therapy in prevention of systemic embolism in patients with atrial fibrillation, valvular heart disease and prosthetic hart valves and in the primary and secondary prevention of venous thromboembolism. They are also used for the prevention of thromboembolic events in patients with acute myocardial infarction and with angina pectoris, in patients with biological hart valves and after some types of orthopaedics surgery. The International Normalized Ratio (INR) is used to evaluate the efficacy of anti-coagulant therapy. The risk of thromboembolic and haemorrhagic complications increases when the INR is out of the therapeutic range. The aim of this study was to present information about the factors influencing activity of oral anticoagulants and interactions between oral anticoagulants and drugs or food. The effect of oral anticoagulants is influenced by genetic and environmental factors such as: medicines, food, diseases and pre-existing conditions. A common mutation in the gene coding for the cytochrome P450 (CYP2C9), with one or more combinations of its polymorphisms, is responsible for the reduced warfarin requirements or for the resistance to warfarin. A mutation in the factor IX is responsible for the risk of bleeding during OAC therapy without excessive prolongation of the prothrombin time (PT). Drugs, herbs and multivitamin supplements can alter the absorption, pharmacokinetics or pharmakodynamics of OAC. Nonsteroid anti-inflammatory drugs and paracetamol in combination with OAC seem to be the most dangerous because they are available without prescription and are used without medical consultation. Patients on OAC therapy are sensitive to changing dietary intake of vitamin K, which is supplied from phylloquinones in plants or from vitamin K-containing medicines. The effect of OAC can be influenced by other existing factors like: fever, diarrhoea, alcohol abuse or physical hyperactivity. Some malignancies

Motion tracking in MR-guided liver therapy by using navigator echoes and projection profile matching.

PubMed

Tokuda, Junichi; Morikawa, Shigehiro; Dohi, Takeyoshi; Hata, Nobuhiko

2004-01-01

Image registration in magnetic resonance (MR) image-guided liver therapy enhances surgical guidance by fusing preoperative multimodality images with intraoperative images, or by fusing intramodality images to correlate serial intraoperative images to monitor the effect of therapy. The objective of this paper is to describe the application of navigator echo and projection profile matching to fast two-dimensional image registration for MR-guided liver therapy. We obtain navigator echoes along the read-out and phase-encoding directions by using modified gradient echo imaging. This registration is made possible by masking out the liver profile from the image and performing profile matching with cross-correlation or mutual information as similarity measures. The set of experiments include a phantom study with a 2.0-T experimental MR scanner, and a volunteer and a clinical study with a 0.5-T open-configuration MR scanner, and these evaluate the accuracy and effectiveness of this method for liver therapy. Both the phantom and volunteer study indicate that this method can perform registration in 34 ms with root-mean-square error of 1.6 mm when the given misalignment of a liver is 30 mm. The clinical studies demonstrate that the method can track liver motion of up to approximately 40 mm. Matching profiles with cross-correlation information perform better than with mutual information in terms of robustness and speed. The proposed image registration method has potential clinical impact on and advantages for MR-guided liver therapy.

Catheter-related thrombosis: biological and clinical evidence for risk with currently available anticoagulants.

PubMed

Montalescot, Gilles; Walenga, Jeanine M

2009-01-01

Anticoagulants used during percutaneous coronary intervention (PCI) should not only prevent coronary events, but also minimize the risk of periprocedural complications. Current anticoagulation therapies for PCI include unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin. UFH and enoxaparin have good efficacy and safety profiles in PCI; furthermore, associated periprocedural complications such as catheter thrombosis are rare. Although newer anticoagulants seem safe and effective in patients with acute coronary syndrome, clinical trial data suggest that some pure factor Xa (FXa) inhibitors are associated with increased rates of catheter thrombosis, compared with heparin-based agents. Experimental systems show that polytherapeutic agents, including UFH and enoxaparin, are more effective anticoagulants than certain single-target agents. More studies are needed to assess whether catheter thrombosis is a class-, drug-, or dose-related effect, and how best to prevent it. Future trials should report the rates of periprocedural complications when assessing the safety of novel anticoagulation therapies in PCI.

Influence of novel oral anticoagulants on anticoagulation care management.

PubMed

Janzic, Andrej; Kos, Mitja

2017-09-01

Anticoagulation treatment was recently improved by the introduction of novel oral anticoagulants (NOACs). Using a combination of qualitative and quantitative methods, this study explores the effects of the introduction of NOACs on anticoagulation care in Slovenia. Face-to-face interviews with key stakeholders revealed evolvement and challenges of anticoagulation care from different perspectives. Obtained information was further explored through the analysis of nationwide data of drug prescriptions and realization of health care services. Simplified management of anticoagulation treatment with NOACs and their high penetration expanded the capacity of anticoagulation clinics, and consequentially the treated population increased by more than 50 % in the last 5 years. The main challenge concerned the expenditures for medicines, which increased approximately 10 times in just a few years. At the same time, the anticoagulation clinics and their core organisation were not affected, which is not expected to change, since they are vital in delivering high-quality care.

Effects of anticoagulant therapy on pregnancy outcomes in patients with thrombophilia and previous poor obstetric history.

PubMed

Mutlu, Ilknur; Mutlu, Mehmet Firat; Biri, Aydan; Bulut, Berk; Erdem, Mehmet; Erdem, Ahmet

2015-04-01

This study investigates the effects of anticoagulant therapy on pregnancy outcomes in 204 patients with thrombophilia and previous poor obstetric outcomes. Patients with poor obstetric history (pre-eclampsia, intrauterine growth retardation, fetal death, placental abruption, recurrent pregnancy loss) and having hereditary thrombophilia were included in this study. Poor obstetric outcomes were observed more frequently in patients who had not taken anticogulant therapy compared with treated group. Live birth rate, gestational age at birth and Apgar scores were significantly higher in the treated group when compared with the untreated group. There were no significant differences in terms of birthweight, mode of delivery and admission rates to the neonatal intensive care unit (NICU). Low-molecular-weight heparin (LMWH) plus acetylsalicylic acid (ASA) had higher gestational age at birth, Apgar scores, live birth rate and a lower abortion rates when compared with controls; in contrast, no significant difference was observed in terms of birthweight, mode of delivery, obstetric complications and admission rates to NICU. There were no significant differences between control group and both LMWH only and ASA only groups in terms of gestational age at birth, Apgar scores, birthweight, mode of delivery, obstetric complications and admission rates to NICU. Only LMWH group had higher live birth rate as compared with control group. The use of only ASA did not seem to affect the perinatal complication rates and outcomes. In conclusion, anticoagulant therapy with both LMWH and ASA seems to provide better obstetric outcomes in pregnant women with thrombophilia and previous poor obstetric outcomes.

Monitoring therapeutic anticoagulation with low molecular weight heparins: is it useful or misleading?

PubMed

Hammerstingl, C

2008-10-01

Weight adapted low molecular weight heparin (LMWH) treatment is recommended as initial anticoagulant therapy of deep vein thrombosis, pulmonary embolism, in patients with myocardial ischemia or when oral anticoagulation (OAC) must be interrupted peri- operatively. Traditionally unfractioned heparin (UFH) was used as standard short acting anticoagulant, with the therapy monitored by frequent laboratory testing. Currently LMWH have broadly replaced UFH as first- choice anticoagulant due to more preferable pharmacokinetics and a better safety profile. Therapeutic anticoagulation with LMWH can be achieved by subcutaneous weight adapted application and measurement of anti-factor Xa- activity (anti-Xa) has been established as gold standard for LMWH- monitoring. However, since almost all LMWH dosing regimens have been developed empirically without laboratory monitoring, there is still a debate ongoing about the usefulness and impact of anti-Xa-testing. Data are lacking that prove a clear correlation between obtained levels of anti-Xa and the patients' clinical outcome. Newer methods have been developed aiming to determine a broader spectrum of LMWH depending anticoagulant activity. Even though there are some promising preliminary results, these alternative methods are not ready for routine clinical use yet. Nevertheless, current guidelines advise determination of anti-Xa in special patient populations with markedly altered LMWH metabolism or to exclude residual LMWH- activity before surgery at very high risk of bleeding. The aim of this article is to review critically the usefulness of anti- Xa guidance of LMWH- therapy and to give new perspectives on upcoming methods of LMWH- monitoring.

Fall risk and anticoagulation for atrial fibrillation in the elderly: A delicate balance.

PubMed

Hagerty, Tracy; Rich, Michael W

2017-01-01

Guidelines for managing atrial fibrillation recommend systemic anticoagulation for almost all patients age 65 and older, but in practice up to 50% of older patients do not receive maintenance anticoagulation therapy. The most common reason physicians cite for withholding anticoagulation in older patients with atrial fibrillation is a perception of a high risk of falling and associated bleeding, especially intracranial hemorrhage. Copyright © 2017 Cleveland Clinic.

Effect of anticoagulation on endothermal ablation of the great saphenous vein.

PubMed

Sharifi, Mohsen; Mehdipour, Mahshid; Bay, Curt; Emrani, Farnaz; Sharifi, Jalaladdin

2011-01-01

A growing number of patients who are on systemic anticoagulation with warfarin require endovenous thermal ablation for reflux disease in the great saphenous vein (GSV). Little is known about the effects of anticoagulation on periprocedural bleeding and long-term closure rates of the treated veins. This study evaluated the effects of uninterrupted anticoagulation in patients undergoing endovenous thermal ablation. In this prospective observational study, 88 limbs of patients on warfarin (anticoagulation group [AG]) who underwent endovenous thermal ablation for GSV reflux disease were compared with 92 limbs in patients receiving no anticoagulation or antiplatelet agents (control group [CG]). Forty percent of AG patients were also receiving antiplatelet therapy. Periprocedural bleeding and closure rate at 1 year were evaluated. No major bleeding occurred in either group. Minor bleeding was noted in 8 of 88 procedures in the AG vs 4 of 92 in the CG (P = 0.24); all in patients receiving radiofrequency ablation. Four of the eight minor bleeds in the AG were noted in patients receiving "triple therapy" with warfarin, aspirin, and clopidogrel or ticlopidine. Triple therapy in the AG was associated with a higher risk of minor bleeding compared with the CG (relative risk, 13.0; 95% confidence interval, 4.10-41.19, P < .001). All treated venous segments remained closed at the 1-year follow-up in both groups. In this relatively small, nonrandomized study comparing endovenous thermal ablation in patients with and without warfarin, no differences were found in periprocedural risk of major bleeding or closure rate of the treated venous segments. Minor bleeding was increased in patients receiving triple therapy with warfarin, aspirin, and a thienopyridine who underwent radiofrequency ablation. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Efficacy and Safety of Oral Anticoagulants Versus Aspirin for Patients With Atrial Fibrillation

PubMed Central

Zhang, Jing-Tao; Chen, Ke-Ping; Zhang, Shu

2015-01-01

Abstract The purpose of this study was to perform a meta-analysis comparing the effectiveness and safety of anticoagulation to antiplatelet therapy for the prevention of thromboembolic events in patients with atrial fibrillation (AF). MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched for studies published through May 31, 2014. Randomized controlled trials comparing anticoagulants (warfarin) and antiplatelet therapy in patients with AF were included. The primary outcomes were the rates of stroke and systemic embolism. Secondary outcomes included the rates of hemorrhage/major bleeding and death. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Nine reports of 8 trials that enrolled 4363 patients (2169 patients received anticoagulation and 2194 antiplatelet therapy) were included. All of the studies compared adjusted-dose warfarin or with aspirin, and the majority of the patients were >70 years of age. Anticoagulants were titrated to an international normalized ratio (INR) of 2.0 to 4.5, and aspirin was administered at a dosage of 75 to 325 mg/d. Death occurred in 206 participants treated with an anticoagulant and 229 participants treated with antiplatelet therapy. There was no significant difference in the overall stroke rate between the groups (OR = 0.667, 95% CI 0.426–1.045, P = 0.08); however, patients with nonrheumatic AF (NRAF) treated with an anticoagulant had a lower risk of stroke (OR = 0.557, 95% CI 0.411–0.753, P < 0.001). Anticoagulants were associated with a lower risk of embolism (OR = 0.616, 95% CI = 0.392–0.966, P = 0.04), and this finding persisted in patients with NRAF (OR = 0.581, 95% CI 0.359–0.941, P = 0.03). No significant difference in the rate of hemorrhage/major bleeding was noted (OR = 1.497, 95% CI 0.730–3.070, P = 0.27), and this finding persisted on subgroup analysis. Anticoagulants appear to be more effective than aspirin in preventing

Benefit of Anticoagulation Therapy in Hyperthyroidism-Related Atrial Fibrillation.

PubMed

Chan, Pak-Hei; Hai, Jojo; Yeung, Chun-Yip; Lip, Gregory Y H; Lam, Karen Siu-Ling; Tse, Hung-Fat; Siu, Chung-Wah

2015-08-01

Existing data on the risk of ischemic stroke in hyperthyroidism-related atrial fibrillation (AF) and the impact of long-term anticoagulation in these patients, particularly those with self-limiting AF, remain inconclusive. Risk of stroke in hyperthyroidism-related AF is the same as nonhyperthyroid counterparts. This was a single-center observational study of 9727 Chinese patients with nonvalvular AF from July 1997 to December 2011. Patients with AF diagnosed concomitantly with hyperthyroidism were identified. Primary and secondary endpoints were defined as hospitalization with ischemic stroke and intracranial hemorrhage in the first 2 years. Patient characteristics, duration of AF, and choice of antithrombotic therapy were recorded. Self-limiting AF was defined as <7 days' duration. Out of 9727 patients, 642 (6.6%) had concomitant hyperthyroidism and AF at diagnosis. For stroke prevention, 136 and 243 patients (21.1% and 37.9%) were prescribed warfarin and aspirin, respectively, whereas the remaining patients (41.0%) received no therapy. Ischemic stroke occurred in 50 patients (7.8%), and no patient developed hemorrhagic stroke. Patients with CHA2 DS2 -VASc of 0 did not develop stroke. Warfarin effectively reduced the incidence of stroke compared with aspirin or no therapy in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF, but not in those with self-limiting AF or CHA2 DS2 -VASc of 0. Presence of hyperthyroidism did not confer additional risk of ischemic stroke compared with nonhyperthyroid AF. Patients with hyperthyroidism-related AF are at high risk of stroke (3.9% per year). Warfarin confers stroke prevention in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF. Overall stroke risk was lower in hyperthyroid non-self-limiting AF patients compared with nonhyperthyroid counterparts. © 2015 Wiley Periodicals, Inc.

Robust inverse-consistent affine CT-MR registration in MRI-assisted and MRI-alone prostate radiation therapy.

PubMed

Rivest-Hénault, David; Dowson, Nicholas; Greer, Peter B; Fripp, Jurgen; Dowling, Jason A

2015-07-01

CT-MR registration is a critical component of many radiation oncology protocols. In prostate external beam radiation therapy, it allows the propagation of MR-derived contours to reference CT images at the planning stage, and it enables dose mapping during dosimetry studies. The use of carefully registered CT-MR atlases allows the estimation of patient specific electron density maps from MRI scans, enabling MRI-alone radiation therapy planning and treatment adaptation. In all cases, the precision and accuracy achieved by registration influences the quality of the entire process. Most current registration algorithms do not robustly generalize and lack inverse-consistency, increasing the risk of human error and acting as a source of bias in studies where information is propagated in a particular direction, e.g. CT to MR or vice versa. In MRI-based treatment planning where both CT and MR scans serve as spatial references, inverse-consistency is critical, if under-acknowledged. A robust, inverse-consistent, rigid/affine registration algorithm that is well suited to CT-MR alignment in prostate radiation therapy is presented. The presented method is based on a robust block-matching optimization process that utilises a half-way space definition to maintain inverse-consistency. Inverse-consistency substantially reduces the influence of the order of input images, simplifying analysis, and increasing robustness. An open source implementation is available online at http://aehrc.github.io/Mirorr/. Experimental results on a challenging 35 CT-MR pelvis dataset demonstrate that the proposed method is more accurate than other popular registration packages and is at least as accurate as the state of the art, while being more robust and having an order of magnitude higher inverse-consistency than competing approaches. The presented results demonstrate that the proposed registration algorithm is readily applicable to prostate radiation therapy planning. Copyright © 2015. Published by

Triple anticoagulation therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention – real life assessment

PubMed Central

Kabłak-Ziembicka, Anna; Bryniarski, Krzysztof; Wrotniak, Leszek; Ostrowska-Kaim, Elżbieta; Żmudka, Krzysztof; Przewłocki, Tadeusz

2016-01-01

Introduction Triple anticoagulation therapy (TT), comprising dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC), is essential in atrial fibrillation (AF) patients after percutaneous coronary intervention (PCI), but it increases the bleeding risk. Aim To assess TT models, in- and out-hospital bleeding and thromboembolic complications, and TT alterations. Material and methods During 12 months, consecutive AF post-PCI patients were scheduled for TT. Alterations in TT and thromboembolic events (death, myocardial infarction, ischemic stroke, in-stent thrombosis, peripheral embolization) were recorded. Major, non-major and minor bleeding episodes were assessed. Results One hundred and thirty-six out of 3171 patients, aged 73.0 ±8.4 years (90 male), were included. Intra-hospitally, thrombotic events occurred in 9 (6.6%), while bleeding events occurred in 71 (52.2%) patients. Access-site hematoma and blood transfusions during in-hospital stay predisposed physicians to heparin administration as part of TT on discharge (p = 0.018 and p = 0.033 respectively). Eventually, DAPT plus warfarin or plus novel oral anticoagulant (NOAC) or plus low molecular weight heparin was prescribed in 72 (52.9%), 53 (39%), and 11 (8.1%) patients, respectively. HAS-BLED and CHA2DS2-VASc scores were similar between subgroups (p = 0.63 and p = 0.64 respectively). During 10.2 ±4.2 months of follow-up, 11 (8.1%) deaths, and 9 (6.6%) non-fatal thromboembolic events occurred. Bleeding events occurred in 45 (34.6%) patients, including 14 (10.3%) major. TT was the only factor associated with increased risk of major bleeding (18.6% vs. 4.2%, p = 0.008). Early termination of any TT component, which concerned 59 (45.4%) patients, did not increase the risk of thromboembolic events (p = 0.89). Conclusions Our study indicates that TT is associated with high mortality and bleeding rates in a relatively short period of time. Discontinuation of any TT drug did not increase the thromboembolic event

Early Transcatheter Aortic Valve Function With and Without Therapeutic Anticoagulation.

PubMed

Hiremath, Pranoti G; Kearney, Kathleen; Smith, Bryn; Don, Creighton; Dvir, Danny; Aldea, Gabriel; Reisman, Mark; McCabe, James M

2017-11-01

Prosthetic leaflet thrombosis is a growing concern in transcatheter aortic valve replacement (TAVR). Given the uncertainty of best practices for antiplatelet and anticoagulation therapies in the post-TAVR period, additional evidence regarding the impact of anticoagulation on prosthetic valve function after TAVR is needed. Patients undergoing native-valve TAVR at a single academic institution between 2012 and 2015 were analyzed based on any anticoagulant use at hospital discharge post TAVR. Changes in prosthetic valve peak velocity and mean gradient were assessed based on transthoracic echocardiograms performed immediately following valve implant and at 4-week follow-up. Multivariate regression analyses were performed to explore the impact of anticoagulation status on early TAVR valve performance. For 403 patients, there were no available data to analyze. Of those, 29.6% were discharged on anticoagulation. Following TAVR, the average mean prosthetic valve gradient was 11.8 ± 5.6 mm Hg and peak velocity was 2.33 ± 0.52 m/s. There were no significant differences between anticoagulated and non-anticoagulated groups in the mean or peak gradients or velocity immediately following implant or at 4 weeks, which remained true following multivariate adjustment (P=.80 for delta mean gradient; P=.91 for delta peak velocity). Our data suggest that the absence of anticoagulation is not associated with short-term degradation in TAVR performance and do not support the routine use of anticoagulation following native-valve TAVR.

Educational and behavioural interventions for anticoagulant therapy in patients with atrial fibrillation.

PubMed

Clarkesmith, Danielle E; Pattison, Helen M; Khaing, Phyo H; Lane, Deirdre A

2017-04-05

Current guidelines recommend oral anticoagulation therapy for patients with atrial fibrillation (AF) with one or more risk factors for stroke; however, anticoagulation control (time in therapeutic range (TTR)) with vitamin K antagonists (VKAs) is dependent on many factors. Educational and behavioural interventions may impact patients' ability to maintain their international normalised ratio (INR) control. This is an updated version of the original review first published in 2013. To evaluate the effects of educational and behavioural interventions for oral anticoagulation therapy (OAT) on TTR in patients with AF. We updated searches from the previous review by searching the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) in The Cochrane Library (January 2016, Issue 1), MEDLINE Ovid (1949 to February week 1 2016), EMBASE Classic + EMBASE Ovid (1980 to Week 7 2016), PsycINFO Ovid (1806 to Week 1 February 2016) and CINAHL Plus with Full Text EBSCO (1937 to 16/02/2016). We applied no language restrictions. We included randomised controlled trials evaluating the effect of any educational and behavioural intervention compared with usual care, no intervention, or intervention in combination with other self-management techniques among adults with AF who were eligible for, or currently receiving, OAT. Two of the review authors independently selected studies and extracted data. Risk of bias was assessed using the Cochrane 'Risk of bias' tool. We included outcome data on TTR, decision conflict (patient's uncertainty in making health-related decisions), percentage of INRs in the therapeutic range, major bleeding, stroke and thromboembolic events, patient knowledge, patient satisfaction, quality of life (QoL), beliefs about medication, illness perceptions, and anxiety and depression. We pooled data for three outcomes - TTR, anxiety and depression, and decision conflict - and reported mean differences (MD). Where

The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) : Exploring the changes in anticoagulant practice in patients with non-valvular atrial fibrillation in the Netherlands.

PubMed

Ten Cate, V; Ten Cate, H; Verheugt, F W A

2016-10-01

There are over 385,000 cases of atrial fibrillation (AF) in the Netherlands, with over 45,000 new cases each year. Among other things, AF patients are at high risk of stroke. Patients are often prescribed oral anticoagulation, such as vitamin K antagonists (VKA), to mitigate these risks. A recently introduced class of oral anticoagulants, non-vitamin K antagonists (NOAC), is quickly gaining currency in global clinical practice. This study provides insight into the changes these new drugs will bring about in Dutch clinical practice.GARFIELD-AF is a large-scale observational AF patient registry initiated in 2009 to track the evolution of global anticoagulation practice, and to study the impact of NOAC therapy in AF in particular. The registry includes a wide array of baseline characteristics and has a particular focus on: (1) bleeding and thromboembolic events; (2) international normalised ratio fluctuations; and (3) therapy compliance and persistence patterns. The results in this paper provide the baseline characteristics of the first cohorts of Dutch participants in this registry and discuss some of the consequences of the changes in anticoagulation practice.Although VKA therapy remains overwhelmingly favoured by Dutch practitioners, NOACs are clearly gaining in popularity. Between 2011 and 2014, NOACs constituted an increasingly large proportion of prescriptions for oral anticoagulants.The insights provided by the GARFIELD-AF registry can be used by healthcare systems to inform better budgetary strategies, by practitioners to better tailor treatment pathways to patients, and finally to promote awareness of the various available treatment options and their associated risks and benefits for patients.

Real-time active MR-tracking of metallic stylets in MR-guided radiation therapy

PubMed Central

Wang, Wei; Dumoulin, Charles L.; Viswanathan, Akila N.; Tse, Zion T. H.; Mehrtash, Alireza; Loew, Wolfgang; Norton, Isaiah; Tokuda, Junichi; Seethamraju, Ravi T.; Kapur, Tina; Damato, Antonio L.; Cormack, Robert A.; Schmidt, Ehud J.

2014-01-01

Purpose To develop an active MR-tracking system to guide placement of metallic devices for radiation therapy. Methods An actively tracked metallic stylet for brachytherapy was constructed by adding printed-circuit micro-coils to a commercial stylet. The coil design was optimized by electromagnetic simulation, and has a radio-frequency lobe pattern extending ~5 mm beyond the strong B0 inhomogeneity region near the metal surface. An MR-tracking sequence with phase-field dithering was used to overcome residual effects of B0 and B1 inhomogeneities caused by the metal, as well as from inductive coupling to surrounding metallic stylets. The tracking system was integrated with a graphical workstation for real-time visualization. 3T MRI catheter-insertion procedures were tested in phantoms and ex-vivo animal tissue, and then performed in three patients during interstitial brachytherapy. Results The tracking system provided high-resolution (0.6 × 0.6 × 0.6 mm3) and rapid (16 to 40 frames per second, with three to one phase-field dithering directions) catheter localization in phantoms, animals, and three gynecologic cancer patients. Conclusion This is the first demonstration of active tracking of the shaft of metallic stylet in MR-guided brachytherapy. It holds the promise of assisting physicians to achieve better targeting and improving outcomes in interstitial brachytherapy. PMID:24903165

Antiplatelet and Anticoagulant Drugs in Interventional Radiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Altenburg, Alexander; Haage, Patrick, E-mail: patrick.haage@helios-kliniken.de

In treating peripheral arterial disease, a profound knowledge of antiplatelet and anticoagulative drug therapy is helpful to assure a positive clinical outcome and to anticipate and avoid complications. Side effects and drug interactions may have fatal consequences for the patient, so interventionalists should be aware of these risks and able to control them. Aspirin remains the first-line agent for antiplatelet monotherapy, with clopidogrel added where dual antiplatelet therapy is required. In case of suspected antiplatelet drug resistance, the dose of clopidogrel may be doubled; prasugrel or ticagrelor may be used alternatively. Glycoprotein IIb/IIIa inhibitors (abciximab or eptifibatide) may help inmore » cases of hypercoagulability or acute embolic complications. Desmopressin, tranexamic acid, or platelet infusions may be used to decrease antiplatelet drug effects in case of bleeding. Intraprocedurally, anticoagulant therapy treatment with unfractionated heparin (UFH) still is the means of choice, although low molecular-weight heparins (LMWH) are suitable, particularly for postinterventional treatment. Adaption of LMWH dose is often required in renal insufficiency, which is frequently found in elderly patients. Protamine sulphate is an effective antagonist for UFH; however, this effect is less for LMWH. Newer antithrombotic drugs, such as direct thrombin inhibitors or factor X inhibitors, have limited importance in periprocedural treatment, with the exception of treating patients with heparin-induced thrombocytopenia (HIT). Nevertheless, knowing pharmacologic properties of the newer drugs facilitate correct bridging of patients treated with such drugs. This article provides a comprehensive overview of antiplatelet and anticoagulant drugs for use before, during, and after interventional radiological procedures.« less

Prescription frequency and predictors for the use of novel direct oral anticoagulants for secondary stroke prevention in the first year after their marketing in Europe--a multicentric evaluation.

PubMed

Luger, Sebastian; Hohmann, Carina; Kraft, Peter; Halmer, Ramona; Gunreben, Ignaz; Neumann-Haefelin, Tobias; Kleinschnitz, Christoph; Walter, Silke; Haripyan, Veronika; Steinmetz, Helmuth; Foerch, Christian; Pfeilschifter, Waltraud

2014-07-01

Direct oral anticoagulants (DOAC) are alternatives to the use of vitamin K antagonists (VKA) as oral anticoagulant therapies to prevent stroke in patients with atrial fibrillation. We assembled a representative secondary prevention cohort from four tertiary care stroke centers to identify factors that independently influence therapeutic decision making 1) not to anticoagulate with either VKA or DOAC and 2) to use DOAC if the patient appears suitable for oral anticoagulant therapy. We identified all patients discharged with the diagnoses 'ischemic stroke' (ICD-10 code I63) or 'transient ischemic attack' (G45) in combination with 'atrial fibrillation' (I48) during 1 year. We performed binary logistic regression analyses to identify factors independently influencing the aforementioned decisions. Our cohort comprised 758 patients. At discharge from the stroke service, 374 patients (49·3%) received oral anticoagulant therapy. Older age, severe stroke, poor recovery in the acute phase, and higher serum creatinine were independent factors to withhold oral anticoagulant therapy, whereas prior oral anticoagulant therapy favored the decision to anticoagulate. Among patients who were anticoagulated, prescription was balanced for VKA (50·3%) and DOAC (49·7%). Renal function and prior oral anticoagulant therapies were the most important factors in this decision. Shortly after their marketing, DOAC are used as frequently as VKA for secondary stroke prevention in patients with atrial fibrillation. The decision between VKA and DOAC is mainly determined by the patient's renal function and the absence or presence of prior oral anticoagulant therapy. © 2014 World Stroke Organization.

Abnormal uterine bleeding in women receiving direct oral anticoagulants for the treatment of venous thromboembolism.

PubMed

Godin, Richard; Marcoux, Violaine; Tagalakis, Vicky

2017-08-01

Abnormal uterine bleeding (AUB) is a common complication of anticoagulant therapy in premenopausal women affected with acute venous thromboembolism. AUB impacts quality of life, and can lead to premature cessation of anticoagulation. There is increasing data to suggest that the direct oral anticoagulants when used for the treatment of venous thromboembolism differ in their menstrual bleeding profile. This article aims to review the existing literature regarding the association between AUB and the direct oral anticoagulants and make practical recommendations. Copyright © 2017 Elsevier Inc. All rights reserved.

MR-guided radiation therapy: transformative technology and its role in the central nervous system

PubMed Central

Tseng, Chia-Lin; Balter, James M.; Teng, Feifei; Parmar, Hemant A.; Sahgal, Arjun

2017-01-01

Abstract This review article describes advancement of magnetic resonance imaging technologies in radiation therapy planning, guidance, and adaptation of brain tumors. The potential for MR-guided radiation therapy to improve outcomes and the challenges in its adoption are discussed. PMID:28380637

Odontostomatologic management of patients receiving oral anticoagulant therapy: a retrospective multicentric study

PubMed Central

2011-01-01

Introduction Today, we frequently find patients taking oral anticoagulant therapy (OAT), a prophylaxis against the occurrence of thromboembolic events. An oral surgeon needs to know how to better manage such patients, in order to avoid hemorrhagic and thromboembolic complications. Materials and methods A group of 193 patients (119 men aged between 46 and 82 and 74 women aged between 54 and 76) undergoing OAT for more than 5 years were managed with a standardized management protocol and a 2-months follow-up. The aim of the present study was to apply a protocol, which could provide a safe intra- and postoperative management of patients on OAT. Results Among the 193 patients, only 2 had postoperative complications. Conclusions We think that the protocol used in the present study can be used for complete safety in the treatment of this type of patients. PMID:21771331

Experimental investigations of an endoluminal ultrasound applicator for MR-guided thermal therapy of pancreatic cancer

NASA Astrophysics Data System (ADS)

Adams, Matthew; Salgaonkar, Vasant; Jones, Peter; Plata, Juan; Chen, Henry; Pauly, Kim Butts; Sommer, Graham; Diederich, Chris

2017-03-01

An MR-guided endoluminal ultrasound applicator has been proposed for palliative and potential curative thermal therapy of pancreatic tumors. Minimally invasive ablation or hyperthermia treatment of pancreatic tumor tissue would be performed with the applicator positioned in the gastrointestinal (GI) lumen, and sparing of the luminal tissue would be achieved with a water-cooled balloon surrounding the ultrasound transducers. This approach offers the capability of conformal volumetric therapy for fast treatment times, with control over the 3D spatial deposition of energy. Prototype endoluminal ultrasound applicators have been fabricated using 3D printed fixtures that seat two 3.2 or 5.6 MHz planar or curvilinear transducers and contain channels for wiring and water flow. Spiral surface coils have been integrated onto the applicator body to allow for device localization and tracking for therapies performed under MR guidance. Heating experiments with a tissue-mimicking phantom in a 3T MR scanner were performed and demonstrated capability of the prototype to perform volumetric heating through duodenal luminal tissue under real-time PRF-based MR temperature imaging (MRTI). Additional experiments were performed in ex vivo pig carcasses with the applicator inserted into the esophagus and aimed towards liver or soft tissue surrounding the spine under MR guidance. These experiments verified the capacity of heating targets up to 20-25 mm from the GI tract. Active device tracking and automated prescription of imaging and temperature monitoring planes through the applicator were made possible by using Hadamard encoded tracking sequences to obtain the coordinates of the applicator tracking coils. The prototype applicators have been integrated with an MR software suite that performs real-time device tracking and temperature monitoring.

Relations of Anticoagulant Therapy with Cognitive Impairment among Patients with Atrial Fibrillation: A Meta-Analysis and Systematic Review.

PubMed

Cheng, Wenke; Liu, Weijun; Li, Bin; Li, Dongfang

2018-03-02

Currently, it is considered that atrial fibrillation (AF) is a risk factor for cognitive impairment and dementia, which is independent of stroke. However, the relationship between anticoagulant drugs and cognitive function in patients with atrial fibrillation is unknown. This study aimed to complete a meta-analysis, and investigate the association between Anticoagulant therapy and cognitive impairment in patients undergoing AF. Two investigators systematically searched the Cochrane Library, PubMed, Embase databases and Web of Science for all studies showing associations. Hazard ratios (HRs) were extracted and pooled. 8 studies included 471057 participants; TTR < 25% vs TTR> 75%; (HR 3.02, 95% CI 1.12-8.91; P=0.03); TTR 25-50% vs TTR> 75% (HR 2.44, 95% CI 0.95-6.22; P=0.06); TTR 50-75% vs TTR> 75% (HR 1.75, 95% CI 0.90-3.99; P=0.1); OAC vs No OAC (HR 0.71, 95% CI.69-0.74; P<0.00001) NOAC vs warfarin (HR0.51, 95% CI0.37-0.71; P<0.00001). Oral anticoagulants (OAC) significantly reduce the occurrence of cognitive impairment in patients with atrial fibrillation. Compared with warfarin, NOAC has an efficiently protective effect on cognition. In the range of INR2-3, with the increase of TTR, the incidence of cognitive impairment is lower.

Health care expenditures and therapeutic outcomes of a pharmacist-managed anticoagulation service versus usual medical care.

PubMed

Hall, Deanne; Buchanan, Julianne; Helms, Bethany; Eberts, Matthew; Mark, Scott; Manolis, Chronis; Peele, Pamela; Docimo, Anne

2011-07-01

To evaluate the differences in health care expenditures and therapeutic outcomes of patients receiving warfarin therapy management by a pharmacist-managed anticoagulation service compared with those receiving warfarin management by usual medical care. Retrospective, matched-cohort study. University of Pittsburgh Medical Center (UPMC) and UPMC Health Plan. Three hundred fifty adults who received warfarin therapy; 175 were managed by the pharmacist-managed anticoagulation service for at least 2 months between October 1, 2007, and September 30, 2008, (case patients) and 175 received usual care (matched comparison group). Medical claims data compared were direct anticoagulation cost and overall medical care costs, anticoagulation-related adverse events, hospitalizations and emergency department visits, frequency of international normalized ratio (INR) testing, and quantity of warfarin refills. Operational costs of the anticoagulation service were also calculated. The INR values and time within therapeutic range were assessed through anticoagulation service reports and laboratory results. The direct anticoagulation care cost was $35,465 versus $111,586 and the overall medical care cost was $754,191 versus $1,480,661 for the anticoagulation service group versus the usual care group. Accounting for operational and drug expenditure costs, the cost savings was $647,024 for the anticoagulation service group. The anticoagulation service group had significantly fewer anticoagulation-related adverse events (14 vs 41, p<0.0001), hospital admissions (3 vs 14, p<0.00001), and emergency department visits (58 vs 134, p<0.00001). The percentage of INR values in range and the percentage of time the INR values were in range were significantly higher in the anticoagulation service group (67.2% vs 54.6%, p<0.0001, and 73.7% vs 61.3%, p<0.0001, respectively). Compared with the usual care group, the anticoagulation service group had significantly more INR tests performed but demonstrated

Use of Percutaneous Aspiration Thrombectomy vs. Anticoagulation Therapy to Treat Acute Iliofemoral Venous Thrombosis: 1-year Follow-up Results of a Randomised, Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cakir, Volkan, E-mail: drvolkancakir@gmail.com; Gulcu, Aytac, E-mail: aytac.gulcu@deu.edu.tr; Akay, Emrah, E-mail: emrahakay@hotmail.com

2014-08-15

PurposeThe purpose of this study was to compare the efficacy of percutaneous aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with anticoagulation therapy alone, for the treatment of acute proximal lower extremity deep vein thrombosis.MethodsIn this randomised, prospective study, 42 patients with acute proximal iliofemoral deep vein thrombosis documented via Doppler ultrasound examination, were separated into an interventional treatment group (16 males, 5 females, average age 51 years) and a medical treatment group (13 males, 8 females, average age 59 years). In the interventional group, PAT with large-lumen 9-F diameter catheterisation was applied, after initiation of standard anticoagulant therapy. Balloon angioplasty (nmore » 19) and stent implementation (n: 14) were used to treat patients with residual stenosis (>50 %) after PAT. Prophylactic IVC filters were placed in two patients. The thrombus clearance status of the venous system was evaluated by venography. In both the medical and interventional groups, venous patency rates and clinical symptom scores were evaluated at months 1, 3, and 12 after treatment.ResultsDeep venous systems became totally cleared of thrombi in 12 patients treated with PAT. The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional and medical treatment groups, respectively. A statistically significant improvement was observed in clinical symptom scores of the interventional group (PAT) with or without stenting (4.23 ± 0.51 before treatment; 0.81 ± 0.92 at month 12) compared with the medical treatment group (4.00 ± 0.63 before treatment; 2.43 ± 0.67 at month 12). During follow-up, four patients in the medical treatment and one in the interventional group developed pulmonary embolisms.ConclusionsFor treatment of acute deep vein thrombosis, PAT with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical

New oral anticoagulants--a review.

PubMed

Ghanima, Waleed; Atar, Dan; Sandset, Per Morten

2013-10-01

Dabigatran, rivaroxaban and apixaban are three new oral anticoagulants that have recently been approved in Norway. The aim of this article is to provide an overview of the mechanisms of action, the most important indications and practical advice on the use of these drugs. The review is based on published phase 3 studies, a literature search in PubMed and the authors' clinical experience. Indications for use of the new anticoagulants include thromboprophylaxis after total hip and knee replacement surgery (all three), prevention of stroke and systemic embolism in non-valvular atrial fibrillation (all three), treatment of acute venous thrombosis and secondary prophylaxis after venous thrombosis (currently only rivaroxaban). For the aforementioned indications, these drugs have proven to be non-inferior to standard established anticoagulation therapy. For atrial fibrillation, all three drugs have also shown a lower incidence of intracranial bleeding compared with standard treatment. It is important to limit the use of these drugs to approved indications, to select patients who show good compliance, to rule out contraindications and to identify drug interactions. Monitoring of coagulation is not required, but patients should be followed up regularly to detect conditions that may lead to changes in the expected efficacy or safety.

MR-ARFI-based method for the quantitative measurement of tissue elasticity: application for monitoring HIFU therapy

NASA Astrophysics Data System (ADS)

Vappou, Jonathan; Bour, Pierre; Marquet, Fabrice; Ozenne, Valery; Quesson, Bruno

2018-05-01

Monitoring thermal therapies through medical imaging is essential in order to ensure that they are safe, efficient and reliable. In this paper, we propose a new approach, halfway between MR acoustic radiation force imaging (MR-ARFI) and MR elastography (MRE), allowing for the quantitative measurement of the elastic modulus of tissue in a highly localized manner. It relies on the simulation of the MR-ARFI profile, which depends on tissue biomechanical properties, and on the identification of tissue elasticity through the fitting of experimental displacement images measured using rapid MR-ARFI. This method was specifically developed to monitor MR-guided high intensity focused ultrasound (MRgHIFU) therapy. Elasticity changes were followed during HIFU ablations (N  =  6) performed ex vivo in porcine muscle samples, and were compared to temperature changes measured by MR-thermometry. Shear modulus was found to increase consistently and steadily a few seconds after the heating started, and such changes were found to be irreversible. The shear modulus was found to increase from 1.49  ±  0.48 kPa (before ablation) to 3.69  ±  0.93 kPa (after ablation and cooling). Thanks to its ability to perform quantitative elasticity measurements in a highly localized manner around the focal spot, this method proved to be particularly attractive for monitoring HIFU ablations.

Early anticoagulation therapy for severe burns complicated by inhalation injury in a rabbit model

PubMed Central

Fu, Zhong-Hua; Guo, Guang-Hua; Xiong, Zhen-Fang; Liao, Xincheng; Liu, Ming-Zhuo; Luo, Jinhua

2017-01-01

The aim of the present study was to determine the effects of early anticoagulation treatment on severe burns complicated by inhalation injury in a rabbit model. Under anesthetization, an electrical burns instrument (100°C) was used to scald the backs of rabbits for 15 sec, which established a 30% III severe burns model. Treatment of the rabbits with early anticoagulation effectively improved the severe burns complicated by inhalation injury-induced lung injury, reduced PaO2, PaCO2 and SPO2 levels, suppressed the expression of tumor necrosis factor-α, interleukin (IL)-1β and IL-6, and increased the activity of IL-10. In addition, it was found that early anticoagulation treatment effectively suppressed the activities of caspase-3 and caspase-9, upregulated the protein expression of vascular endothelial growth factor (VEGF) and decreased the protein expression of protease-activated receptor 1 (PAR1) in the severe burns model. It was concluded that early anticoagulation treatment affected the severe burns complicated by inhalation injury in a rabbit model through the upregulation of VEGF and downregulation of PAR1 signaling pathways. Thus, early anticoagulation is a potential therapeutic option for severe burns complicated by inhalation injury. PMID:28944866

Towards integration of PET/MR hybrid imaging into radiation therapy treatment planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paulus, Daniel H., E-mail: daniel.paulus@imp.uni-erlangen.de; Thorwath, Daniela; Schmidt, Holger

2014-07-15

Purpose: Multimodality imaging has become an important adjunct of state-of-the-art radiation therapy (RT) treatment planning. Recently, simultaneous PET/MR hybrid imaging has become clinically available and may also contribute to target volume delineation and biological individualization in RT planning. For integration of PET/MR hybrid imaging into RT treatment planning, compatible dedicated RT devices are required for accurate patient positioning. In this study, prototype RT positioning devices intended for PET/MR hybrid imaging are introduced and tested toward PET/MR compatibility and image quality. Methods: A prototype flat RT table overlay and two radiofrequency (RF) coil holders that each fix one flexible body matrixmore » RF coil for RT head/neck imaging have been evaluated within this study. MR image quality with the RT head setup was compared to the actual PET/MR setup with a dedicated head RF coil. PET photon attenuation and CT-based attenuation correction (AC) of the hardware components has been quantitatively evaluated by phantom scans. Clinical application of the new RT setup in PET/MR imaging was evaluated in anin vivo study. Results: The RT table overlay and RF coil holders are fully PET/MR compatible. MR phantom and volunteer imaging with the RT head setup revealed high image quality, comparable to images acquired with the dedicated PET/MR head RF coil, albeit with 25% reduced SNR. Repositioning accuracy of the RF coil holders was below 1 mm. PET photon attenuation of the RT table overlay was calculated to be 3.8% and 13.8% for the RF coil holders. With CT-based AC of the devices, the underestimation error was reduced to 0.6% and 0.8%, respectively. Comparable results were found within the patient study. Conclusions: The newly designed RT devices for hybrid PET/MR imaging are PET and MR compatible. The mechanically rigid design and the reproducible positioning allow for straightforward CT-based AC. The systematic evaluation within this study

Identification of Reduced-Order Thermal Therapy Models Using Thermal MR Images: Theory and Validation

PubMed Central

2013-01-01

In this paper, we develop and validate a method to identify computationally efficient site- and patient-specific models of ultrasound thermal therapies from MR thermal images. The models of the specific absorption rate of the transduced energy and the temperature response of the therapy target are identified in the reduced basis of proper orthogonal decomposition of thermal images, acquired in response to a mild thermal test excitation. The method permits dynamic reidentification of the treatment models during the therapy by recursively utilizing newly acquired images. Such adaptation is particularly important during high-temperature therapies, which are known to substantially and rapidly change tissue properties and blood perfusion. The developed theory was validated for the case of focused ultrasound heating of a tissue phantom. The experimental and computational results indicate that the developed approach produces accurate low-dimensional treatment models despite temporal and spatial noises in MR images and slow image acquisition rate. PMID:22531754

Identification of reduced-order thermal therapy models using thermal MR images: theory and validation.

PubMed

Niu, Ran; Skliar, Mikhail

2012-07-01

In this paper, we develop and validate a method to identify computationally efficient site- and patient-specific models of ultrasound thermal therapies from MR thermal images. The models of the specific absorption rate of the transduced energy and the temperature response of the therapy target are identified in the reduced basis of proper orthogonal decomposition of thermal images, acquired in response to a mild thermal test excitation. The method permits dynamic reidentification of the treatment models during the therapy by recursively utilizing newly acquired images. Such adaptation is particularly important during high-temperature therapies, which are known to substantially and rapidly change tissue properties and blood perfusion. The developed theory was validated for the case of focused ultrasound heating of a tissue phantom. The experimental and computational results indicate that the developed approach produces accurate low-dimensional treatment models despite temporal and spatial noises in MR images and slow image acquisition rate.

The Population-Based Long-Term Impact of Anticoagulant and Antiplatelet Therapies in Low-Risk Patients With Atrial Fibrillation.

PubMed

Golive, Anjani; May, Heidi T; Bair, Tami L; Jacobs, Victoria; Crandall, Brian G; Cutler, Michael J; Day, John D; Mallender, Charles; Osborn, Jeffrey S; Stevens, Scott M; Weiss, J Peter; Woller, Scott C; Bunch, T Jared

2017-07-01

Among patients with atrial fibrillation (AF), the risk of stroke risk is a significant concern. CHADS 2 and CHA 2 DS 2 -VASc ≤2 scoring have been used to stratify patients into categories of risk. Without randomized, prospective data, the need and type of long-term antithrombotic medications for thromboembolism prevention in lower risk AF patients remains controversial. We sought to define the long-term impact of anticoagulant and antiplatelet therapy use in AF patients at low risk of stroke. A total of 56,764 patients diagnosed with AF and a CHADS 2 score of 0 or 1, or CHA 2 DS 2 -VASc score of 0, 1, or 2 were studied. Antithrombotic therapy was defined as aspirin, clopidogrel (antiplatelet therapy), or warfarin monotherapy (anticoagulation) initiated within 6 months of AF diagnosis. End points included all-cause mortality, cerebrovascular accident, transient ischemic attack (TIA), and major bleed. The average age of the population was 67.0 ± 14.1 years and 56.6% were male. In total, 9,682 received aspirin, 1,802 received clopidogrel, 1,164 received warfarin, and 46,042 did not receive any antithrombotic therapy. Event rates differed between patients with a CHADS 2 score of 0 and 1; 18.5% and 37.8% had died, 1.7% and 3.4% had a stroke, 2.2% and 3.2% had a TIA, and 14% and 12.5% had a major bleed, respectively (p <0.0001 for all). The rates of stroke, TIA, and major bleeding increased as antithrombotic therapy intensity increased from no therapy, to aspirin, to clopidogrel, and to warfarin (all p <0.0001). Similar outcomes were observed in low-risk CHA 2 DS 2 -VASc scores (0 to 2). In low-risk AF patients with a CHADS 2 score of 0 to 1 or CHA 2 DS 2 -VASc score of 0 to 2, the use of aspirin, clopidogrel, and warfarin was not associated with lower stroke rates at 5 years compared with no therapy. However, the use of antithrombotic agents was associated with a significant risk of bleed. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of renal function deterioration on adverse events during anticoagulation therapy using non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

PubMed

Miyamoto, Koji; Aiba, Takeshi; Arihiro, Shoji; Watanabe, Makoto; Kokubo, Yoshihiro; Ishibashi, Kohei; Hirose, Sayako; Wada, Mitsuru; Nakajima, Ikutaro; Okamura, Hideo; Noda, Takashi; Nagatsuka, Kazuyuki; Noguchi, Teruo; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kamakura, Shiro; Shimizu, Wataru; Miyamoto, Yoshihiro; Toyoda, Kazunori; Kusano, Kengo

2016-08-01

Renal function is crucial for patients with non-valvular atrial fibrillation (NVAF) using non-vitamin K antagonist oral anticoagulants (NOAC). The incidence of renal function deterioration during anticoagulation therapy and its impact of adverse events are unknown. In 807 consecutive NVAF patients treated with NOAC and with estimated creatinine clearance (eCCr) ≥ 50 ml/min (mean age 68 ± 11 years, mean CHADS2 score = 1.8 ± 1.4, CHA2DS2-VASc score = 2.8 ± 1.8, HAS-BLED score = 1.7 ± 1.1), we analyzed the time course of renal function and clinical outcomes, and compared these with the data of general Japanese inhabitants from the Suita Study (n = 2140). Of the 807 patients, 751 (93 %) maintained eCCr ≥ 50 ml/min (group A) whereas the remaining 56 (7 %) fell into the eCCr < 50 ml/min (group B) during the 382 ± 288 days of follow-up. Multivariate logistic regression analysis revealed that advanced age, lower body weight, and congestive heart failure were independent predictors for renal function deterioration in patients with eCCr ≥ 50 ml/min at baseline. Major and/or minor bleedings were more commonly observed in group B than in group A (21 vs. 8 %; P = 0.0004). The CHADS2, CHA2DS2-VASc, and HAS-BLED scores were also significant predictors of renal function deterioration (P < 0.0001). The incidences of renal function deterioration were 1.4, 3.4, 10.5 and 11.7 % in patients with CHADS2 score of 0, 1, 2 and ≥3, respectively. As to CHA2DS2-VASc score, renal function deterioration occurred in 0, 1.7, 9.8 and 15.0 % with a score of 0, 1-2, 3-4 and ≥5, respectively. In the Suita Study of the general population, on the other hand, 122 of 2140 participants with eCCr ≥ 50 ml/min at baseline (5.7 %) fell into the eCCr < 50 ml/min during about 2 years. The incidence of renal function deterioration increased with the CHADS2 score in the general population as well as in our patients. Renal function deterioration was

Anticoagulants and the propagation phase of thrombin generation.

PubMed

Orfeo, Thomas; Gissel, Matthew; Butenas, Saulius; Undas, Anetta; Brummel-Ziedins, Kathleen E; Mann, Kenneth G

2011-01-01

The view that clot time-based assays do not provide a sufficient assessment of an individual's hemostatic competence, especially in the context of anticoagulant therapy, has provoked a search for new metrics, with significant focus directed at techniques that define the propagation phase of thrombin generation. Here we use our deterministic mathematical model of tissue-factor initiated thrombin generation in combination with reconstructions using purified protein components to characterize how the interplay between anticoagulant mechanisms and variable composition of the coagulation proteome result in differential regulation of the propagation phase of thrombin generation. Thrombin parameters were extracted from computationally derived thrombin generation profiles generated using coagulation proteome factor data from warfarin-treated individuals (N = 54) and matching groups of control individuals (N = 37). A computational clot time prolongation value (cINR) was devised that correlated with their actual International Normalized Ratio (INR) values, with differences between individual INR and cINR values shown to derive from the insensitivity of the INR to tissue factor pathway inhibitor (TFPI). The analysis suggests that normal range variation in TFPI levels could be an important contributor to the failure of the INR to adequately reflect the anticoagulated state in some individuals. Warfarin-induced changes in thrombin propagation phase parameters were then compared to those induced by unfractionated heparin, fondaparinux, rivaroxaban, and a reversible thrombin inhibitor. Anticoagulants were assessed at concentrations yielding equivalent cINR values, with each anticoagulant evaluated using 32 unique coagulation proteome compositions. The analyses showed that no anticoagulant recapitulated all features of warfarin propagation phase dynamics; differences in propagation phase effects suggest that anticoagulants that selectively target fXa or thrombin may

Anticoagulant and Antiplatelet Prescribing Patterns for Patients with Atrial Fibrillation after Percutaneous Coronary Intervention.

PubMed

Woods, Erin A; Ackman, Margaret L; Graham, Michelle M; Koshman, Sheri L; Boswell, Rosaleen M; Barry, Arden R

2016-01-01

Current guidelines recommend triple antithrombotic therapy (TAT), defined as acetylsalicylic acid (ASA), clopidogrel, and warfarin, for patients with nonvalvular atrial fibrillation who have undergone percutaneous coronary intervention with stent implantation. The choice of anticoagulant/antiplatelet therapy in this population is ambiguous and complex, and prescribing patterns are not well documented. To characterize local prescribing patterns for anticoagulant/antiplatelet therapy after percutaneous coronary intervention in patients with nonvalvular atrial fibrillation. A chart review was conducted at a single quaternary cardiology centre. Patients with nonvalvular atrial fibrillation were identified via medical records, and those who underwent percutaneous coronary intervention were identified using a local clinical patient registry. Adult inpatients with nonvalvular atrial fibrillation and a CHADS2 score (based on congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) of 1 or higher who underwent percutaneous coronary intervention from 2011 to 2013 were included. Patients undergoing cardiovascular surgery or transcatheter aortic valve replacement, those with mechanical devices requiring anticoagulation, and those with an allergy to any component of TAT were excluded. Seventy patients were included. The median age was 75 years, and 52 (74%) were men. At discharge, 30 (43%) were receiving TAT and 27 (39%) were receiving dual antiplatelet therapy (clopidogrel and ASA). No patients received the combination of warfarin and clopidogrel. Among those who received TAT, 90% (19 of 21) who received a bare metal stent had a recommended duration of 1 month, and 75% (6 of 8) who received a drug-eluting stent had a recommended duration of 1 year. Direct-acting oral anticoagulants with 2 antiplatelet drugs were prescribed for 9% (6 of 70) of the patients, and 10% (7 of 70) received ticagrelor and ASA with or without warfarin. Overall, the

Lupus anticoagulants and antiphospholipid antibodies

MedlinePlus

Blood clots - lupus anticoagulants; DVT - anticoagulants ... Most often, lupus anticoagulants and aPL are found in people with diseases such as systemic lupus erythematosus (SLE). Lupus anticoagulants and ...

MR guided FUS therapy with a Robotic Assistance System

NASA Astrophysics Data System (ADS)

Jenne, Jürgen W.; Krafft, Axel J.; Maier, Florian; Rauschenberg, Jaane; Semmler, Wolfhard; Huber, Peter E.; Bock, Michael

2009-04-01

Magnetic Resonance imaging guided Focus Ultrasound Surgery (MRgFUS) is a highly precise method to ablate tissue non-invasively. To date, there is only one commercial MRgFUS system available and only a few are in a prototype stage. The objective of this ongoing project is to establish an MRgFUS therapy unit as add-on for a commercially available robotic assistance system originally designed for percutaneous needle interventions in whole-body MR scanners.

Non anti-coagulant factors associated with filter life in continuous renal replacement therapy (CRRT): a systematic review and meta-analysis.

PubMed

Brain, Matthew; Winson, Elizabeth; Roodenburg, Owen; McNeil, John

2017-02-20

Optimising filter life and performance efficiency in continuous renal replacement therapy has been a focus of considerable recent research. Larger high quality studies have predominantly focussed on optimal anticoagulation however CRRT is complex and filter life is also affected by vascular access, circuit and management factors. We performed a systematic search of the literature to identify and quantify the effect of vascular access, circuit and patient factors that affect filter life and presented the results as a meta-analysis. A systematic review and meta-analysis was performed by searching Pubmed (MEDLINE) and Ovid EMBASE libraries from inception to 29 th February 2016 for all studies with a comparator or independent variable relating to CRRT circuits and reporting filter life. Included studies documented filter life in hours with a comparator other than anti-coagulation intervention. All studies comparing anticoagulation interventions were searched for regression or hazard models pertaining to other sources of variation in filter life. Eight hundred nineteen abstracts were identified of which 364 were selected for full text analysis. 24 presented data on patient modifiers of circuit life, 14 on vascular access modifiers and 34 on circuit related factors. Risk of bias was high and findings are hypothesis generating. Ranking of vascular access site by filter longevity favours: tunnelled semi-permanent catheters, femoral, internal jugular and subclavian last. There is inconsistency in the difference reported between femoral and jugular catheters. Amongst published literature, modality of CRRT consistently favoured continuous veno-venous haemodiafiltration (CVVHD-F) with an associated 44% lower failure rate compared to CVVH. There was a trend favouring higher blood flow rates. There is insufficient data to determine advantages of haemofilter membranes. Patient factors associated with a statistically significant worsening of filter life included mechanical

Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy.

PubMed

Zhang, Zhongheng; Hongying, Ni

2012-01-01

Regional citrate anticoagulation (RCA) is an attractive anticoagulation mode in continuous renal replacement therapy (CRRT) because it restricts the anticoagulatory effect to the extracorporeal circuit. In recent years, several randomized controlled trials have been conducted to investigate its superiority over other anticoagulation modes. Thus, we performed a systematic review of available evidence on the efficacy and safety of RCA. A systematic review of randomized controlled trials investigating the efficacy and safety of RCA was performed. PubMed, Current Contents, CINAHL, and EMBASE databases were searched to identify relevance articles. Data on circuit life span, bleeding events, metabolic derangement, and mortality were abstracted. Mean difference was used for continuous variables, and risk ratio was used for binomial variables. The random effects or fixed effect model was used to combine these data according to heterogeneity. The software Review Manager 5.1 was used for the meta-analysis. Six studies met our inclusion criteria, which involved a total of 658 circuits. In these six studies patients with liver failure or a high risk of bleeding were excluded. The circuit life span in the RCA group was significantly longer than that in the control group, with a mean difference of 23.03 h (95% CI 0.45-45.61 h). RCA was able to reduce the risk of bleeding, with a risk ratio of 0.28 (95% CI 0.15-0.50). Metabolic stability (electrolyte and acid-base stabilities) in performing RCA was comparable to that in other anticoagulation modes, and metabolic derangements (hypernatremia, metabolic alkalosis, and hypocalcemia) could be easily controlled without significant clinical consequences. Two studies compared mortality rate between RCA and control groups, with one reported similar mortality rate and the other reported superiority of RCA over the control group (hazards ratio 0.7). RCA is effective in maintaining circuit patency and reducing the risk of bleeding, and thus

Stroke prevention with oral anticoagulation in older people with atrial fibrillation - a pragmatic approach.

PubMed

Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H

2012-08-01

With advancing age, the prevalence of both stroke and non valvular atrial fibrillation (NVAF) is increasing. NVAF in old age has a high embolic potential if not anticoagulated. Oral anticoagulation therapy is cost effective in older people with NVAF due to their high base line stroke risk. The current stroke and bleeding risk scoring schemes have been based on complex scoring systems that are difficult to apply in clinical practice. Both scoring schemes include similar risk factors for ischemic and bleeding events which may lead to confusion in clinical decision making to balance the risks of bleeding against the risks of stroke, thereby limiting the applicability of such schemes. The difficulty in application of such schemes combined with physicians' fear of inducing bleeding complications has resulted in under use of anticoagulation therapy in older people. As older people (≥75 years) with NVAF are all at high risk of stroke, we are suggesting a pragmatic approach based on a yes/no decision rather than a risk scoring stratification which involves an opt out rather an opt in approach unless there is a contraindication for oral anticoagulation. Antiplatelet agents should not be an alternative option for antithrombotic treatment in older people with NVAF due to lack of efficacy and the potential of being used as an excuse of not prescribing anticoagulation. Bleeding risk should be assessed on individual basis and the decision to anticoagulate should include patients' views.

Stroke Prevention with Oral Anticoagulation in Older People with Atrial Fibrillation - A Pragmatic Approach

PubMed Central

Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H

2012-01-01

With advancing age, the prevalence of both stroke and non valvular atrial fibrillation (NVAF) is increasing. NVAF in old age has a high embolic potential if not anticoagulated. Oral anticoagulation therapy is cost effective in older people with NVAF due to their high base line stroke risk. The current stroke and bleeding risk scoring schemes have been based on complex scoring systems that are difficult to apply in clinical practice. Both scoring schemes include similar risk factors for ischemic and bleeding events which may lead to confusion in clinical decision making to balance the risks of bleeding against the risks of stroke, thereby limiting the applicability of such schemes. The difficulty in application of such schemes combined with physicians’ fear of inducing bleeding complications has resulted in under use of anticoagulation therapy in older people. As older people (≥75 years) with NVAF are all at high risk of stroke, we are suggesting a pragmatic approach based on a yes/no decision rather than a risk scoring stratification which involves an opt out rather an opt in approach unless there is a contraindication for oral anticoagulation. Antiplatelet agents should not be an alternative option for antithrombotic treatment in older people with NVAF due to lack of efficacy and the potential of being used as an excuse of not prescribing anticoagulation. Bleeding risk should be assessed on individual basis and the decision to anticoagulate should include patients’ views. PMID:23185715

WE-FG-BRA-07: Theranostic Nanoparticles Improve Clinical MR-Guided Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Detappe, A; Institut Lumiere-Matiere, Lyon, FR; Kunjachan, S

Purpose: MR-guided radiation therapy is a current and emerging clinical reality. We have designed and tested a silica-based gadolinium chelates nanoparticle (AGuIX) for integration with MR-guided radiation therapy. The AGuIX nanoparticles used in this study are a dual-modality probe with radiosensitization properties and better MRI contrast than current FDA-approved gadolinium chelates. In advance of an approved Phase I clinical trial, we report on the efficacy and safety in multiple animal models and clinically relevant radiation conditions. By modeling our study on current clinic workflows, we show compatibility with modern patient care, thus heightening the translational significance of this research. Methods:more » The dual imaging and therapy functionality of AGuIX was investigated in mice with clinical radiation beams while safety was evaluated in mice, and nonhuman primates after systemic injection of 0.25 mg/g of nanoparticles. MRI/ICP-MS were used to measure tumor uptake and biodistribution. Due to their small size (2–3 nm), AGuIX have good renal clearance (t1/2=19min). We performed in vitro cell uptake quantification and radiosensitization studies (clonogenic assays and DNA damage quantification). In vivo radiation therapy studies were performed with both 6MV and 6MV-FFF clinical radiation beams. Histology was performed to measure the increase in DNA damage in the tumor and to evaluate the toxicity in healthy tissues. Results: In vitro and in vivo results demonstrate statistically significant increase (P < 0.01) in DNA damage, tumor growth supression and survival (+100 days) compared to radiation alone. Negligible toxicity was observed in all of the animal models. The combination of 6MV-FFF/AGuIX demonstrated a substantial dose enhancement compared to 6MV/AGuIX (DEF = 1.36 vs. 1.22) due to the higher proportion of low energy photons. Conclusion: With demonstrated efficacy and negligible toxicity in mice and non-human primates, AGuIX is a biocompatible

TU-B-210-00: MR-Guided Focused Ultrasound Therapy in Oncology

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

MR guided focused ultrasound (MRgFUS), or alternatively high-intensity focused ultrasound (MRgHIFU), is approved for thermal ablative treatment of uterine fibroids and pain palliation in bone metastases. Ablation of malignant tumors is under active investigation in sites such as breast, prostate, brain, liver, kidney, pancreas, and soft tissue. Hyperthermia therapy with MRgFUS is also feasible, and may be used in conjunction with radiotherapy and for local targeted drug delivery. MRI allows in situ target definition and provides continuous temperature monitoring and subsequent thermal dose mapping during HIFU. Although MRgHIFU can be very precise, treatment of mobile organs is challenging and advancedmore » techniques are required because of artifacts in MR temperature mapping, the need for intercostal firing, and need for gated HIFU or tracking of the lesion in real time. The first invited talk, “MR guided Focused Ultrasound Treatment of Tumors in Bone and Soft Tissue”, will summarize the treatment protocol and review results from treatment of bone tumors. In addition, efforts to extend this technology to treat both benign and malignant soft tissue tumors of the extremities will be presented. The second invited talk, “MRI guided High Intensity Focused Ultrasound – Advanced Approaches for Ablation and Hyperthermia”, will provide an overview of techniques that are in or near clinical trials for thermal ablation and hyperthermia, with an emphasis of applications in abdominal organs and breast, including methods for MRTI and tracking targets in moving organs. Learning Objectives: Learn background on devices and techniques for MR guided HIFU for cancer therapy Understand issues and current status of clinical MRg HIFU Understand strategies for compensating for organ movement during MRgHIFU Understand strategies for strategies for delivering hyperthermia with MRgHIFU CM - research collaboration with Philips.« less

Review of economics and cost-effectiveness analyses of anticoagulant therapy for stroke prevention in atrial fibrillation in the US.

PubMed

von Schéele, Birgitta; Fernandez, Maria; Hogue, Susan Lynn; Kwong, Winghan Jacqueline

2013-05-01

To summarize the available evidence on the issues in health economics related to oral anticoagulation for stroke prevention in atrial fibrillation (AF) in the US. A literature review was performed using PubMed, EMBASE, Cochrane Library, and International Pharmaceutical Abstracts, as well as the websites of professional organizations. The search was conducted according to a prespecified protocol, limiting articles to those published in English from 2001 to October 2012 and focused on the economics associated with AF and AF-related stroke in the US. Data from 27 studies were extracted and included in the review. Strokes in patients with AF are more debilitating and have higher recurrence rates and mortality compared with strokes unrelated to AF. However, data describing the long-term cost of AF-related stroke and stroke subtypes remain limited. The costs of major gastrointestinal (GI) bleeding and intracranial bleeding related to warfarin are significant, whereas the costs of the more frequent minor GI bleeding are relatively low. Overall, the cost-effectiveness of warfarin versus aspirin or no treatment in patients with at least 1 risk factor for stroke is well established. Economic evaluations based on results from randomized controlled clinical trials generally found that new anticoagulants were a cost-effective alternative to warfarin for stroke prevention in AF. However, these cost-effectiveness results are highly sensitive to how well optimal international normalized ratio control is maintained (within target of 2.0-3.0) for warfarin and the time horizon used for analysis. Time in therapeutic range for warfarin in routine clinical practice was lower than in clinical trials, as shown by previous studies. This review identified several areas of uncertainty regarding the economic benefit of anticoagulants. The generalizability of cost-effectiveness results of anticoagulant therapy in AF based on clinical trial data must be confirmed by comparative effectiveness

Practical recommendations for the choice of anticoagulants in the management of patients with atrial fibrillation on ibrutinib.

PubMed

Chai, Khai Li; Rowan, Gail; Seymour, John F; Burbury, Kate; Carney, Dennis; Tam, Constantine S

2017-12-01

The management of AF represents a major challenge in patients with CLL, especially in elderly patients with multiple comorbidities who are representative of the majority of patients with CLL. This is especially complex in the case of ibrutinib. Many anticoagulants have potential for pharmacological interaction with ibrutinib, and ibrutinib itself has antiplatelet properties. Use of ibrutinib therapy in these patients mandates review and revision of the need for anticoagulation and best anticoagulant to use. Herein, we review the current knowledge of the metabolism of common anticoagulants and how they may interact with ibrutinib.

High-b-value diffusion-weighted MR imaging for pretreatment prediction and early monitoring of tumor response to therapy in mice.

PubMed

Roth, Yiftach; Tichler, Thomas; Kostenich, Genady; Ruiz-Cabello, Jesus; Maier, Stephan E; Cohen, Jack S; Orenstein, Arie; Mardor, Yael

2004-09-01

To evaluate the use of diffusion-weighted magnetic resonance (MR) imaging with standard and high b values for pretreatment prediction and early detection of tumor response to various antineoplastic therapies in an animal model. Mice bearing C26 colon carcinoma tumors were treated with doxorubicin (n = 25) and with aminolevulinic acid-based photodynamic therapy (n = 23). Fourteen mice served as controls. Conventional T2-weighted fast spin-echo and diffusion-weighted MR images were acquired once before therapy and at 6, 24, and 48 hours after treatment. Pretreatment and early (1-2 days) posttreatment water diffusion parameters were calculated and compared with later changes in tumor volumes measured on conventional MR images by using the Pearson correlation test. In chemotherapy-treated tumors, a significant correlation (P <.002, r = 0.6) was observed between diffusion parameters that reflected tumor viability, measured prior to treatment, and changes in tumor volumes after therapy. This correlation implies that tumors with high pretreatment viability will respond better to chemotherapy than more necrotic tumors. In tumors treated with photodynamic therapy, no such correlation was found. Changes observed in water diffusion 1-2 days after treatment significantly correlated with later tumor growth rate for both therapies (P <.002, r = 0.54 for photodynamic therapy; P <.0003, r = 0.61 for chemotherapy). High-b-value diffusion-weighted MR imaging has potential use for the early detection of response to therapy and for predicting treatment outcome prior to initiation of chemotherapy. Copyright RSNA, 2004

Antithrombotic Therapy for Atrial Fibrillation

PubMed Central

You, John J.; Singer, Daniel E.; Howard, Patricia A.; Lane, Deirdre A.; Eckman, Mark H.; Fang, Margaret C.; Hylek, Elaine M.; Schulman, Sam; Go, Alan S.; Hughes, Michael; Spencer, Frederick A.; Manning, Warren J.; Halperin, Jonathan L.

2012-01-01

Background: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS2 score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS2 score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized

Target specific oral anticoagulants in the management of thromboembolic disease in the elderly.

PubMed

Maddula, Surekha; Ansell, Jack

2013-08-01

The elderly population represents a population at highest risk of thromboembolism, but also the most vulnerable to hemorrhage. In the community setting there is a general tendency to under- treat this patient group. Specific consideration must be taken with elderly patients because they have reduced renal function, co-morbidities and risk of falls, altered pharmacodynamics, and challenges with adherence. Vitamin K antagonists, most often warfarin, have been the first line choice of therapy for long-term anticoagulation and enjoyed an unopposed position in the market for the last 70 years. Recently several new oral anticoagulants have been developed and found to be equally effective as warfarin in phase III studies and may provide an optimal treatment option in the elderly population. In this review we explore the target-specific oral anticoagulants and the pharmacological differences between them with a focus on the elderly population in whom these new drugs would constitute a possible alternative to warfarin therapy.

Impact of clinical pharmacist intervention in anticoagulation clinic in Sudan.

PubMed

Ahmed, Nahid Osman; Osman, Bashier; Abdelhai, Yassein Mohamed; El-Hadiyah, Tariq Muhammed Hashim

2017-08-01

Background Many trials have compared anticoagulation management provided by a pharmacist led anticoagulation clinic versus usual physician care showing the role for clinical pharmacist in the management of anticoagulant therapy, and demonstrating excellent outcomes. In Sudan, there is no published research evaluating the role of pharmacist in providing pharmaceutical care for patients taking warfarin. Objective The objective of the study is to assess the role of clinical pharmacist intervention in warfarin patients compared to usual medical care. Setting This study was conducted in Ahmed Gasim cardiac surgery and renal transplant center warfarin clinic. Methods One hundred thirty-five patients were randomly selected from adult patients on warfarin therapy The history of INR records, and adverse effects for the past year, were recorded. Then patients' warfarin dose adjustments according to INR, was done by the clinical pharmacist for one year. Patients received continuous verbal education and written information about warfarin. Main outcome measure The primary outcome for this study was the INR control, while the secondary outcomes were the bleeding events and hospitalization due to warfarin. Results After the clinical pharmacist intervention there was significant (P < 0.01) improvement in INR control and a significant (P < 0.05) reduction in incidence of bleeding after clinical pharmacist intervention. Hospitalization due to warfarin related complications (bleeding, high INR, low INR) was also significantly (P < 0.001) reduced. Conclusion Clinical pharmacists intervention in warfarin therapy improve INR control, reduce bleeding and hospitalization due to warfarin complications.

Real-life Use of Anticoagulants in Venous Thromboembolism With a Focus on Patients With Exclusion Criteria for Direct Oral Anticoagulants.

PubMed

Moustafa, Farès; Pesavento, Raffaele; di Micco, Pierpaolo; González-Martínez, José; Quintavalla, Roberto; Peris, Maria-Luisa; Porras, José Antonio; Falvo, Nicolas; Baños, Pilar; Monreal, Manuel

2018-04-01

We assessed the real-life use of direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and exclusion criteria for randomized trials. From 2013 to 2016, 3,578 of 18,853 patients (19%) had exclusion criteria. Irrespective of which anticoagulant was chosen, they had more VTE recurrences (hazard ratio (HR): 3.10; 95% confidence interval (CI): 2.47-3.88), major bleeds (HR: 4.10; 95% CI: 3.38-4.96), and deaths (HR: 9.47; 95% CI: 8.46-10.6) than those without exclusion criteria. During initial therapy, no patient with exclusion criteria on DOACs (n = 115) recurred, but those on rivaroxaban bled less often (adjusted HR: 0.18; 95% CI: 0.04-0.79) than those on unfractionated heparin (n = 224) and similar to those (n = 3,172) on low-molecular-weight (LMWH) heparin. For long-term therapy, patients on rivaroxaban (n = 151) had nonsignificantly fewer VTE recurrences (adjusted HR: 0.74; 95% CI: 0.08-1.32) and major bleeds (adjusted HR: 0.41; 95% CI: 0.15-1.15) than those on LMWH (n = 2,071). The efficacy and safety of DOACs were similar to standard therapy. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Injuries and outcomes associated with traumatic falls in the elderly population on oral anticoagulant therapy.

PubMed

Boltz, Melissa M; Podany, Abigail B; Hollenbeak, Christopher S; Armen, Scott B

2015-09-01

Fall risk for older adults is a multi-factorial public health problem as 90% of geriatric injuries are caused by traumatic falls. The CDC estimated 33% of adults >65 years incurred a fall in 2011, with 30% resulting in moderate injury. While much has been written about overall risk to trauma patients on oral anticoagulant (OAC) therapy, less has been reported on outcomes in the elderly trauma population. We used data from the National Trauma Data Bank (NTDB) to identify the types of injury and complications incurred, length of stay, and mortality associated with OACs in elderly patients sustaining a fall. Using standard NTDB practices, data were collected on elderly patients (≥65 years) on OACs with diagnosis of fall as the primary mechanism of injury from 2007 to 2010. Univariate analysis was used to determine patient variables influencing risk of fall on OACs. Odds ratios were calculated for types of injury sustained and post-trauma complications. Logistic regression was used to determine mortality associated with type of injury incurred. Of 118,467 elderly patients sampled, OAC use was observed in 444. Predisposing risk factors for fall on OACs were >1 comorbidity (p<0.0001). Patients on OACs were 188% and 370% more likely to develop 2 and >3 complications (p<0.0001); the most significant being ARDS and ARF (p<0.0001). The mortality rate on OACs was 16%. Injuries to the GI tract, liver, spleen, and kidney (p<0.0002) were more likely to occur. However, if patients suffered a mortality, the most significant injuries were skull fractures and intracranial haemorrhage (p<0.0001). Risks of anticoagulation in elderly trauma patients are complex. While OAC use is a predictor of 30-day mortality after fall, the injuries sustained are markedly different between the elderly who die and those who do not. As a result there is a greater need for healthcare providers to identify preventable and non-preventable risks factors indicative of falls in the anti-coagulated elderly

Secondary prevention of recurrent venous thromboembolism after initial oral anticoagulation therapy in patients with unprovoked venous thromboembolism.

PubMed

Robertson, Lindsay; Yeoh, Su Ern; Ramli, Ahmad

2017-12-15

Currently, little evidence is available on the length and type of anticoagulation used for extended treatment for prevention of recurrent venous thromboembolism (VTE) in patients with unprovoked VTE who have completed initial oral anticoagulation therapy. To compare the efficacy and safety of available oral therapeutic options (aspirin, warfarin, direct oral anticoagulants (DOACs)) for extended thromboprophylaxis in adults with a first unprovoked VTE, to prevent VTE recurrence after completion of an acceptable initial oral anticoagulant treatment period, as defined in individual studies. For this review, the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (March 2017) as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2). We also searched trials registries (March 2017) and reference lists of relevant articles. We included randomised controlled trials in which patients with a first, symptomatic, objectively confirmed, unprovoked VTE, who had been initially treated with anticoagulants, were randomised to extended prophylaxis (vitamin K antagonists (VKAs), antiplatelet agents, or DOACs) versus no prophylaxis or placebo. We also included trials that compared one type of extended prophylaxis versus another type of extended prophylaxis. Two review authors independently selected studies, assessed quality, and extracted data. We resolved disagreements by discussion. Six studies with a combined total of 3436 participants met the inclusion criteria. Five studies compared extended prophylaxis versus placebo: three compared warfarin versus placebo, and two compared aspirin versus placebo. One study compared one type of extended prophylaxis (rivaroxaban) versus another type of extended prophylaxis (aspirin). For extended prophylaxis versus placebo, we downgraded the quality of the evidence for recurrent VTE and all-cause mortality to moderate owing to concerns arising from risks of selection and performance bias

Oral Anticoagulation in Patients With Liver Disease.

PubMed

Qamar, Arman; Vaduganathan, Muthiah; Greenberger, Norton J; Giugliano, Robert P

2018-05-15

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Differences in attitude, education, and knowledge about oral anticoagulation therapy among patients with atrial fibrillation in Europe: result of a self-assessment patient survey conducted by the European Heart Rhythm Association.

PubMed

Hernández Madrid, Antonio; Potpara, Tatjana S; Dagres, Nikolaos; Chen, Jian; Larsen, Torben B; Estner, Heidi; Todd, Derick; Bongiorni, Maria G; Sciaraffia, Elena; Proclemer, Alessandro; Cheggour, Saida; Amara, Walid; Blomstrom-Lundqvist, Carina

2016-03-01

The purpose of this patient survey was to analyse the knowledge about blood thinning medications relative to gender, age, education, and region of residence in patients with atrial fibrillation (AF). A total of 1147 patients with AF [mean age 66 ± 13 years, 529 (45%) women] from eight European countries responded to this survey. Most patients understood that the indication for anticoagulation therapy was to 'thin the blood', but 8.1% responded that the purpose of the medication was to treat the arrhythmia. Patients with college or university grades reported less frequent deviations from their target INR range compared with those without schooling (2.8% vs. 5.1%, P < 0.05). The awareness of anticoagulation-related risk of bleedings was lowest in patients without schooling (38.5%) and highest in those with college and university education (57.0%), P < 0.05. The same pattern was also observed regarding patient's awareness of non-vitamin K antagonist oral anticoagulants (NOACs): 56.5% of the patients with university education and only 20.5% of those without schooling (P < 0.05) knew about NOACs, indicating that information about new anticoagulation therapies remains well below the target. Bleeding events were statistically less frequent in patients on NOACs compared with vitamin K antagonists. The education level and patients' knowledge have a direct influence on the global management of the anticoagulation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Rectal cancer: assessment of complete response to preoperative combined radiation therapy with chemotherapy--conventional MR volumetry versus diffusion-weighted MR imaging.

PubMed

Curvo-Semedo, Luís; Lambregts, Doenja M J; Maas, Monique; Thywissen, Thomas; Mehsen, Rana T; Lammering, Guido; Beets, Geerard L; Caseiro-Alves, Filipe; Beets-Tan, Regina G H

2011-09-01

To determine diagnostic performance of diffusion-weighted (DW) magnetic resonance (MR) imaging for assessment of complete tumor response (CR) after combined radiation therapy with chemotherapy (CRT) in patients with locally advanced rectal cancer (LARC) by means of volumetric signal intensity measurements and apparent diffusion coefficient (ADC) measurements and to compare the performance of DW imaging with that of T2-weighted MR volumetry. A retrospective analysis of 50 patients with LARC, for whom clinical and imaging data were retrieved from a previous imaging study approved by the local institutional ethical committee and for which all patients provided informed consent, was conducted. Patients underwent pre- and post-CRT standard T2-weighted MR and DW MR. Two independent readers placed free-hand regions of interest (ROIs) in each tumor-containing section on both data sets to determine pre- and post-CRT tumor volumes and tumor volume reduction rates (volume). ROIs were copied to an ADC map to calculate tumor ADCs. Histopathologic findings were the standard of reference. Receiver operating characteristic (ROC) curves were generated to compare performance of T2-weighted and DW MR volumetry and ADC. The intraclass correlation coefficient (ICC) was used to evaluate interobserver variability and the correlation between T2-weighted and DW MR volumetry. Areas under the ROC curve (AUCs) for identification of a CR that was based on pre-CRT volume, post-CRT volume, and volume, respectively, were 0.57, 0.70, and 0.84 for T2-weighted MR versus 0.63, 0.93, and 0.92 for DW MR volumetry (P = .15, .02, .42). Pre- and post-CRT ADC and ADC AUCs were 0.55, 0.54, and 0.51, respectively. Interobserver agreement was excellent for all pre-CRT measurements (ICC, 0.91-0.96) versus good (ICC, 0.61-0.79) for post-CRT measurements. ICC between T2-weighted and DW MR volumetry was excellent (0.97) for pre-CRT measurements versus fair (0.25) for post-CRT measurements. Post-CRT DW MR

Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice?

PubMed

Go, Alan S; Hylek, Elaine M; Chang, Yuchiao; Phillips, Kathleen A; Henault, Lori E; Capra, Angela M; Jensvold, Nancy G; Selby, Joe V; Singer, Daniel E

2003-11-26

Warfarin has been shown to be highly efficacious for preventing thromboembolism in atrial fibrillation in randomized trials, but its effectiveness and safety in clinical practice is less clear. To evaluate the effect of warfarin on risk of thromboembolism, hemorrhage, and death in atrial fibrillation within a usual care setting. Cohort study assembled between July 1, 1996, and December 31, 1997, and followed up through August 31, 1999. Large integrated health care system in Northern California. Of 13,559 adults with nonvalvular atrial fibrillation, 11,526 were studied, 43% of whom were women, mean age 71 years, with no known contraindications to anticoagulation at baseline. Ischemic stroke, peripheral embolism, hemorrhage, and death according to warfarin use and comorbidity status, as determined by automated databases, review of medical records, and state mortality files. Among 11,526 patients, 397 incident thromboembolic events (372 ischemic strokes, 25 peripheral embolism) occurred during 25,341 person-years of follow-up, and warfarin therapy was associated with a 51% (95% confidence interval [CI], 39%-60%) lower risk of thromboembolism compared with no warfarin therapy (either no antithrombotic therapy or aspirin) after adjusting for potential confounders and likelihood of receiving warfarin. Warfarin was effective in reducing thromboembolic risk in the presence or absence of risk factors for stroke. A nested case-control analysis estimated a 64% reduction in odds of thromboembolism with warfarin compared with no antithrombotic therapy. Warfarin was also associated with a reduced risk of all-cause mortality (adjusted hazard ratio, 0.69; 95% CI, 0.61-0.77). Intracranial hemorrhage was uncommon, but the rate was moderately higher among those taking vs those not taking warfarin (0.46 vs 0.23 per 100 person-years, respectively; P =.003, adjusted hazard ratio, 1.97; 95% CI, 1.24-3.13). However, warfarin therapy was not associated with an increased adjusted risk of

Evaluating the impact of new anticoagulants in the hospital setting

PubMed Central

Braidy, Nady; Bui, Khai; Bajorek, Beata

2010-01-01

The short-comings of current anticoagulants have led to the development of newer, albeit more expensive, oral alternatives. Objective To explore the potential impact the new anticoagulants dabigatran and rivaroxaban in the local hospital setting, in terms of utilisation and subsequent costing. Method A preliminary costing analysis was performed based on a prospective 2-week clinical audit (29th June - 13th July 2009). Data regarding current anticoagulation management were extracted from the medical files of patients admitted to Ryde Hospital. To model potential costing implications of using the newer agents, the reported incidence of VTE/stroke and bleeding events were obtained from key clinical trials. Results Data were collected for 67 patients treated with either warfarin (n=46) or enoxaparin (n=21) for prophylaxis of VTE/stroke. At least two-thirds of all patients were deemed suitable candidates for the use of newer oral anticoagulants (by current therapy: warfarin: 65.2% (AF), 34.8% (VTE); enoxaparin: 100%, (VTE)). The use of dabigatran in VTE/stroke prevention was found to be more cost- effective than warfarin and enoxaparin due to significantly lower costs of therapeutic monitoring and reduced administration costs. Rivaroxaban was more cost-effective than warfarin and enoxaparin for VTE/stroke prevention when supplier-rebates (33%) were factored into costing. Conclusion This study highlights the potential cost- effectiveness of newer anticoagulants, dabigatran and rivaroxaban, compared to warfarin and enoxaparin. These agents may offer economic advantages, as well as clinical benefits, in the hospital-based management of anticoagulated patients. PMID:25132883

ANMCO Position Paper: the use of non-vitamin K dependent new oral anticoagulant(s) in pulmonary embolism therapy and prevention

PubMed Central

Roncon, Loris; Azzarito, Michele; Becattini, Cecilia; Bongarzoni, Amedeo; Casazza, Franco; Cuccia, Claudio; D’Agostino, Carlo; Rugolotto, Matteo; Vatrano, Marco; Vinci, Eugenio; Fenaroli, Paride; Formigli, Dario; Silvestri, Paolo; Nardi, Federico; Vedovati, Maria Cristina; Scherillo, Marino

2017-01-01

Abstract The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prevention of thromboembolic pulmonary embolism. The authors of this position paper face, in succession, issues concerning NOACs, including (i) their mechanism of action, pharmacodynamics, and pharmacokinetics; (ii) the use in the acute phase with the ‘double drug single dose’ approach or with ‘single drug double dose’; (iii) the use in the extended phase with demonstrated efficacy and with low incidence of bleeding events; (iv) the encouraging use of NOACs in particular subgroups of patients such as those with cancer, the ones under- or overweight, with renal insufficiency (creatinine clearance > 30 mL/min), the elderly (>75 years); (v) they propose a possible laboratory clinical pathway for follow-up; and (vi) carry out an examination on the main drug interactions, their potential bleeding risk, and the way to deal with some bleeding complications. The authors conclude that the use of NOACs both in the acute phase and in the extended phase is equally effective to conventional therapy and associated with fewer major bleeding events, which make their use in patients at higher risk of recurrences safer. PMID:28751847

Protein C deficiency related obscure gastrointestinal bleeding treated by enteroscopy and anticoagulant therapy.

PubMed

Hsu, Wei-Fan; Tsang, Yuk-Ming; Teng, Chung-Jen; Chung, Chen-Shuan

2015-01-21

Obscure gastrointestinal bleeding is an uncommonly encountered and difficult-to-treat clinical problem in gastroenterology, but advancements in endoscopic and radiologic imaging modalities allow for greater accuracy in diagnosing obscure gastrointestinal bleeding. Ectopic varices account for less than 5% of all variceal bleeding cases, and jejunal variceal bleeding due to extrahepatic portal hypertension is rare. We present a 47-year-old man suffering from obscure gastrointestinal bleeding. Computed tomography of the abdomen revealed multiple vascular tufts around the proximal jejunum but no evidence of cirrhosis, and a visible hypodense filling defect suggestive of thrombus was visible in the superior mesenteric vein. Enteroscopy revealed several serpiginous varices in the proximal jejunum. Serologic data disclosed protein C deficiency (33.6%). The patient was successfully treated by therapeutic balloon-assisted enteroscopy and long-term anticoagulant therapy, which is normally contraindicated in patients with gastrointestinal bleeding. Diagnostic modalities for obscure gastrointestinal bleeding, such as capsule endoscopy, computed tomography enterography, magnetic resonance enterography, and enteroscopy, were also reviewed in this article.

Eculizumab in paroxysmal nocturnal hemoglobinuria with Budd-Chiari syndrome progressing despite anticoagulation

PubMed Central

2012-01-01

Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive, life-threatening disorder characterized by chronic intravascular hemolysis caused by uncontrolled complement activation. Hepatic vein thrombosis (Budd-Chiari syndrome) is common in PNH patients. This case report describes the response to eculizumab (a humanized monoclonal antibody that inhibits terminal complement activation) in a 25-year-old male with progressive liver function deterioration despite standard anticoagulation therapy and transjugular intrahepatic porto-systemic shunt. The patient presented with anemia, severe thrombocytopenia, headache, abdominal pain, and distention. He was diagnosed with PNH, cerebral vein thrombosis, and Budd-Chiari syndrome. Despite adequate anticoagulation, diuretic administration, and placement of a transjugular shunt, additional thrombotic events and progressive liver damage were observed. Eculizumab therapy was initiated, resulting in rapid blockade of intravascular hemolysis, increased platelet counts, ascites resolution, and liver function recovery, all of which are presently sustained. Since starting eculizumab the patient has had no further thrombotic events and his quality of life has dramatically improved. This is the first report to confirm the role of complement-mediated injury in the progression of Budd-Chiari syndrome in a patient with PNH. This case shows that terminal complement blockade with eculizumab can reverse progressive thromboses and hepatic failure that is unresponsive to anticoagulation therapy and suggests that early initiation of eculizumab should be included in the therapeutic regimen of patients with PNH-related Budd-Chiari syndrome. PMID:23210433

Timing of oral anticoagulant therapy in acute ischemic stroke with atrial fibrillation: study protocol for a registry-based randomised controlled trial.

PubMed

Åsberg, Signild; Hijazi, Ziad; Norrving, Bo; Terént, Andreas; Öhagen, Patrik; Oldgren, Jonas

2017-12-02

Oral anticoagulation therapy is recommended for the prevention of recurrent ischemic stroke in patients with atrial fibrillation (AF). Current guidelines do not provide evidence-based recommendations on optimal time-point to start anticoagulation therapy after an acute ischemic stroke. Non-vitamin K antagonist oral anticoagulants (NOACs) may offer advantages compared to warfarin because of faster and more predictable onset of action and potentially a lower risk of intracerebral haemorrhage also in the acute phase after an ischemic stroke. The TIMING study aims to establish the efficacy and safety of early vs delayed initiation of NOACs in patients with acute ischemic stroke and AF. The TIMING study is a national, investigator-led, registry-based, multicentre, open-label, randomised controlled study. The Swedish Stroke Register is used for enrolment, randomisation and follow-up of 3000 patients, who are randomised (1:1) within 72 h from ischemic stroke onset to either early (≤ 4 days) or delayed (≥ 5-10 days) start of NOAC therapy. The primary outcome is the composite of recurrent ischemic stroke, symptomatic intracerebral haemorrhage, or all-cause mortality within 90 days after randomisation. Secondary outcomes include: individual components of the primary outcome at 90 and 365 days; major haemorrhagic events; functional outcome by the modified Rankin Scale at 90 days; and health economics. In an optional biomarker sub-study, blood samples will be collected after randomisation from approximately half of the patients for central analysis of cardiovascular biomarkers after study completion. The study is funded by the Swedish Medical Research Council. Enrolment of patients started in April 2017. The TIMING study addresses the ongoing clinical dilemma of when to start NOAC after an acute ischemic stroke in patients with AF. By the inclusion of a randomisation module within the Swedish Stroke Register, the advantages of a prospective randomised study design

Current issues in patient adherence and persistence: focus on anticoagulants for the treatment and prevention of thromboembolism

PubMed Central

Kneeland, Patrick P; Fang, Margaret C

2010-01-01

Warfarin therapy reduces morbidity and mortality related to thromboembolism. Yet adherence to long-term warfarin therapy remains challenging due to the risks of anticoagulant-associated complications and the burden of monitoring. The aim of this paper is to review determinants of adherence and persistence on long-term anticoagulant therapy for atrial fibrillation and venous thromboembolism. We evaluate what the current literature reveals about the impact of warfarin on quality of life, examine warfarin trial data for patterns of adherence, and summarize known risk factors for warfarin discontinuation. Studies suggest only modest adverse effects of warfarin on quality of life, but highlight the variability of individual lifestyle experiences of patients on warfarin. Interestingly, clinical trials comparing anticoagulant adherence to alternatives (such as aspirin) show that discontinuation rates on warfarin are not consistently higher than in control arms. Observational studies link a number of risk factors to warfarin non-adherence including younger age, male sex, lower stroke risk, poor cognitive function, poverty, and higher educational attainment. In addition to differentiating the relative impact of warfarin-associated complications (such as bleeding) versus the lifestyle burdens of warfarin monitoring on adherence, future investigation should focus on optimizing patient education and enhancing models of physician–patient shared-decision making around anticoagulation. PMID:20361065

Delphi-RAND consensus of the Spanish Society of Internal Medicine on the controversies in anticoagulant therapy and prophylaxis in medical diseases. INTROMBIN Project (Uncertainty in thromboprophylaxis in internal medicine).

PubMed

Ruiz-Ruiz, F; Medrano, F J; Navarro-Puerto, M A; Rodríguez-Torres, P; Romero-Alonso, A; Santos-Lozano, J M; Alonso-Ortiz Del Rio, C; Varela-Aguilar, J M; Calderón, E J; Marín-León, I

2018-05-21

The aim of this study was to determine the opinion of internists on the management of anticoagulation and thromboembolism prophylaxis in complex clinical scenarios in which the risk-benefit ratio of surgery is narrow and to develop a consensus document on the use of drugs anticoagulant therapy in this patient group. To this end, we identified by consensus the clinical areas of greatest uncertainty, a survey was created with 20 scenarios laid out in 40 clinical questions, and we reviewed the specific literature. The survey was distributed among the internists of the Spanish Society of Internal Medicine (SEMI) and was completed by 290 of its members. The consensus process was implemented by changing the Delphi-RAND appropriateness method in an anonymous, double-round process that enabled an expert panel to identify the areas of agreement and uncertainty. In our case, we also added the survey results to the panel, a methodological innovation that helps provide additional information on the standard clinical practice. The result of the process is a set of 19 recommendations formulated by SEMI experts, which helps establish guidelines for action on anticoagulant therapy in complex scenarios (high risk or active haemorrhage, short life expectancy, coexistence of antiplatelet therapy or comorbidities such as kidney disease and liver disease), which are not uncommon in standard clinical practice. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

A pharmacoeconomic study of traditional anticoagulation versus direct oral anticoagulation for the treatment of venous thromboembolism in the emergency department.

PubMed

Law, Stephanie; Ghag, Daljit; Grafstein, Eric; Stenstrom, Robert; Harris, Devin

2016-09-01

Patients with venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [PE]) are commonly treated as outpatients. Traditionally, patients are anticoagulated with low-molecular-weight heparin (LMWH) and warfarin, resulting in return visits to the ED. The direct oral anticoagulant (DOAC) medications do not require therapeutic monitoring or repeat visits; however, they are more expensive. This study compared health costs, from the hospital and patient perspectives, between traditional versus DOAC therapy. A chart review of VTE cases at two tertiary, urban hospitals from January 1, 2010 to December 31, 2012 was performed to capture historical practice in VTE management, using LMWH/warfarin. This historical data were compared against data derived from clinical trials, where a DOAC was used. Cost minimization analyses comparing the two modes of anticoagulation were completed from hospital and patient perspectives. Of the 207 cases in the cohort, only 130 (63.2%) were therapeutically anticoagulated (international normalized ratio 2.0-3.0) at emergency department (ED) discharge; patients returned for a mean of 7.18 (range: 1-21) visits. Twenty-one (10%) were admitted to the hospital; 4 (1.9%) were related to VTE or anticoagulation complications. From a hospital perspective, a DOAC (in this case, rivaroxaban) had a total cost avoidance of $1,488.04 per VTE event, per patient. From a patient perspective, it would cost an additional $204.10 to $349.04 over 6 months, assuming no reimbursement. VTE management in the ED has opportunities for improvement. A DOAC is a viable and cost-effective strategy for VTE treatment from a hospital perspective and, depending on patient characteristics and values, may also be an appropriate and cost-effective option from a patient perspective.

Acute Pulmonary Embolism in Emergency Department Patients Despite Therapeutic Anticoagulation.

PubMed

Liu, Michelle Y; Ballard, Dustin W; Huang, Jie; Rauchwerger, Adina S; Reed, Mary E; Bouvet, Sean C; Vinson, David R

2018-05-01

-day outcomes included one major hemorrhage and one additional death. No patients experienced recurrent or worsening VTE. We found a low prevalence of therapeutic anticoagulation at the time of acute PE diagnosis. Most patients with breakthrough PE underwent a change in therapy, though management varied widely. Subtherapeutic anticoagulation levels in the preceding weeks were common and support the importance of anticoagulation adherence.

Balancing between bleeding and thromboembolism after percutaneous coronary intervention in patients with atrial fibrillation. Could triple anticoagulant therapy be a solution?

PubMed

Dąbrowska, Magdalena; Ochała, Andrzej; Cybulski, Wiesław; Tendera, Michał

2013-01-01

Atrial fibrillation (AF) has nowadays become a common disease as it comes along with medical procedures propagation in the ageing population with coexistent diseases. Hence a need for use of combined anticoagulant and antithrombotic therapy has arisen. According to the 2010 ESC guidelines on myocardial revascularization, short-term triple antithrombotic therapy after percutaneous coronary intervention (PCI) should be given if compelling indications exist. To assess bleeding and thromboembolic events depending on the antithrombotic regimen in short- and long-term follow-up in patients with AF after PCI with stent implantation. A 12-month prospective, non-randomized registry was conducted in the 3(rd) Department of Cardiology in the Upper Silesian Medical Center in Katowice from October 2008 to April 2011. One hundred and four patients in two groups - on triple therapy (TT; aspirin + clopidogrel + vitamin K antagonists (VKA; warfarin or acenocoumarol) n = 44) and on dual therapy (DT; aspirin + clopidogrel; n = 60) - were assessed 30 days and 12 months after angioplasty. All bleeding events occurred more often in the triple anticoagulated group in 30 days (TT 20.5% vs. DT 6.7%; p = 0.03) and after 12 months (TT 38.9% vs. DT 17.2%, p = 0.09). The difference in major bleeding events was not significant after 30 days (TT 9.1% vs. DT 3.3%; p = NS) or 12 months (TT 11.1% vs. DT 6.9%; p = NS). Thromboembolic events after 30 days (DT 5.0% vs. TT 2.3%) and 12 months (TT 11.1% vs. DT 3.4%) were comparable. The percentage of deaths after 30 days (DT 1.7% vs. TT 0.0%, p = NS) increased after 12 months (DT 13.8% vs. TT 0.0%, p = 0.09). Significantly higher risk of bleeding on TT becomes blurred by a tendency to increased mortality in patients on DT.

Recent developments in separation of low molecular weight heparin anticoagulants.

PubMed

Sadowski, Radosław; Gadzała-Kopciuch, Renata; Buszewski, Bogusław

2017-10-05

The general function of anticoagulants is to prevent blood clotting and growing of the existing clots in blood vessels. In recent years, there has been a significant improvement in developing methods of prevention as well as pharmacologic and surgical treatment of thrombosis. For over the last two decades, low molecular weight heparins (LMWHs) have found their application in the antithrombotic diseases treatment. These types of drugs are widely used in clinical therapy. Despite the biological and medical importance of LMWHs, they have not been completely characterized in terms of their chemical structure. Due to both, the structural complexity of these anticoagulants and the presence of impurities, their structural characterization requires the employment of advanced analytical techniques. Since separation techniques play the key role in these endeavors, this review will focus on the presentation of recent developments in the separation of LMWH anticoagulants. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cross-cultural adaptation and psychometric properties of the Brazilian-Portuguese version of the Duke Anticoagulation Satisfaction Scale.

PubMed

Pelegrino, Flávia M; Dantas, Rosana A S; Corbi, Inaiara S A; da Silva Carvalho, Ariana R; Schmidt, André; Pazin Filho, Antônio

2012-09-01

The aim of this study was to evaluate the internal reliability and validity of the Brazilian-Portuguese version of Duke Anticoagulation Satisfaction Scale (DASS) among cardiovascular patients. Oral anticoagulation is widely used to prevent and treat thromboembolic events in several conditions, especially in cardiovascular diseases; however, this therapy can induce dissatisfaction and reduce the quality of life. Methodological and cross-sectional research design. The cultural adaptation of the DASS included the translation and back-translation, discussions with healthcare professionals and patients to ensure conceptual equivalence, semantic evaluation and instrument pretest. The Brazilian-Portuguese version of the DASS was tested among subjects followed in a university hospital anticoagulation outpatient clinic. The psychometric properties were assessed by construct validity (convergent, known groups and dimensionality) and internal consistency/reliability (Cronbach's alpha). A total of 180 subjects under oral anticoagulation formed the baseline validation population. DASS total score and SF-36 domain correlations were moderate for General health (r=-0.47, p<0.01), Vitality (r=-0.44, p<0.01) and Mental health (r=-0.42, p<0.01) (convergent). Age and length on oral anticoagulation therapy (in years) were weakly correlated with total DASS score and most of the subscales, except Limitation (r=-0.375, p<0.01) (Known groups). The Cronbach's alpha coefficient was 0.79 for the total scale, and it ranged from 0.76 (hassles and burdens)-0.46 (psychological impact) among the domains, confirming the internal consistency reliability. The Brazilian-Portuguese version of the DASS has shown levels of reliability and validity comparable with the original English version. Healthcare practitioners and researchers need internationally validated measurement tools to compare outcomes of interventions in clinical management and research tools in oral anticoagulation therapy. © 2011

Heparin bridge therapy and post-polypectomy bleeding

PubMed Central

Kubo, Toshiyuki; Yamashita, Kentaro; Onodera, Kei; Iida, Tomoya; Arimura, Yoshiaki; Nojima, Masanori; Nakase, Hiroshi

2016-01-01

AIM To identify risk factors for post-polypectomy bleeding (PPB), focusing on antithrombotic agents. METHODS This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonoscopic hot polypectomies, endoscopic mucosal resections and endoscopic submucosal dissections performed between January 2011 and December 2014 were reviewed. RESULTS PPB occurred in 29 (3.7%) of 788 polypectomies performed during the study period. Antiplatelet or anticoagulant agents were prescribed for 210 (26.6%) patients and were ceased before polypectomy except for aspirin and cilostazol in 19 cases. Bridging therapy using intravenous unfractionated heparin was adopted for 73 patients. The univariate analysis revealed that anticoagulants, heparin bridge, and anticoagulants plus heparin bridge were significantly associated with PPB (P < 0.0001) whereas antiplatelets and antiplatelets plus heparin were not. None of the other factors including age, gender, location, size, shape, number of resected polyps, prophylactic clipping and resection method were correlated with PPB. The multivariate analysis demonstrated that anticoagulants and anticoagulants plus heparin bridge therapy were significant risk factors for PPB (P < 0.0001). Of the 29 PPB cases, 4 required transfusions and none required surgery. A thromboembolic event occurred in a patient who took anticoagulant. CONCLUSION Patients taking anticoagulants have an increased risk of PPB, even if the anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants. PMID:28018108

Heparin bridge therapy and post-polypectomy bleeding.

PubMed

Kubo, Toshiyuki; Yamashita, Kentaro; Onodera, Kei; Iida, Tomoya; Arimura, Yoshiaki; Nojima, Masanori; Nakase, Hiroshi

2016-12-07

To identify risk factors for post-polypectomy bleeding (PPB), focusing on antithrombotic agents. This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonoscopic hot polypectomies, endoscopic mucosal resections and endoscopic submucosal dissections performed between January 2011 and December 2014 were reviewed. PPB occurred in 29 (3.7%) of 788 polypectomies performed during the study period. Antiplatelet or anticoagulant agents were prescribed for 210 (26.6%) patients and were ceased before polypectomy except for aspirin and cilostazol in 19 cases. Bridging therapy using intravenous unfractionated heparin was adopted for 73 patients. The univariate analysis revealed that anticoagulants, heparin bridge, and anticoagulants plus heparin bridge were significantly associated with PPB ( P < 0.0001) whereas antiplatelets and antiplatelets plus heparin were not. None of the other factors including age, gender, location, size, shape, number of resected polyps, prophylactic clipping and resection method were correlated with PPB. The multivariate analysis demonstrated that anticoagulants and anticoagulants plus heparin bridge therapy were significant risk factors for PPB ( P < 0.0001). Of the 29 PPB cases, 4 required transfusions and none required surgery. A thromboembolic event occurred in a patient who took anticoagulant. Patients taking anticoagulants have an increased risk of PPB, even if the anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants.

The effect of the amiodarone-warfarin interaction on anticoagulation quality in a single, high-quality anticoagulation center.

PubMed

White, Ryan D; Riggs, Kyle W; Ege, Ed J; Petroski, Gregory F; Koerber, Scott M; Flaker, Greg

2016-03-01

Clinical trials have reported a low time in therapeutic range (TTR) in patients with atrial fibrillation treated with both warfarin andamiodarone. These trials included centers and countries with both high and low TTRs. What is the impact of amiodarone on the TTR in a single, high-quality anticoagulation clinic? TTR was assessed in amiodarone and nonamiodarone-treated patients from a University anticoagulation clinic. Baseline characteristics between patients ever-taking or never-taking amiodarone were similar, except more amiodarone patients were smokers (19.5 vs. 6.1%, P = 0.0031). The TTR calculated from 8901international normalized ratios (INRs) in 249 nonamiodarone patients with a mean follow-up of 34 ± 20 months (mean INR 36 ± 18) was 66 ± 16.6% compared with 61.3 ± 16.2% (P = 0.111) from 1455 INRs in 41 amiodarone-treated patients with a mean follow-up of 28 ± 20 months (mean INR 35 ± 22). Factors associated with a low TTR were male sex (P = 0.0013), smoker (P = 0.0048), and amiodarone use (P = 0.0374). A second on-treatment analysis, in which the TTR was calculated only during amiodarone therapy, resulted in similar findings; however, amiodarone did not emerge as a predictor of a low TTR. In 11 patients, the TTR prior to amiodarone (54.5 ± 22.2%) was not significantly different in the first 3 months (54.6 ± 33.4%) or after 3 months (67.2 ± 33.7%) of amiodarone. In a single high-quality anticoagulation center, anticoagulation quality, as measured by the TTR, can be comparable in amiodarone and nonamiodarone-treated patients.

Pharmacogenetics of novel oral anticoagulants: a review of identified gene variants & future perspectives.

PubMed

Ašić, Adna; Marjanović, Damir; Mirat, Jure; Primorac, Dragan

2018-05-16

Novel oral anticoagulants (NOACs) are becoming a therapy of choice in everyday clinical practice after almost 50 years during which warfarin and related coumarin derivatives were used as the main anticoagulants. Advantages of NOACs over standard anticoagulants include their predictable pharmacodynamics and pharmacokinetics, stable plasma concentrations and less drug-drug and food-drug interactions. However, pharmacogenetics has its place in administration of NOACs, as considerable interindividual variations have been detected. In this review, previous findings in pharmacogenetics of dabigatran, rivaroxaban, apixaban and edoxaban are summarized, along with recommendations for studying genes encoding metabolically important enzymes for four selected NOACs. Future directions include identification of clinically relevant SNPs, and change in optimum dosage for patients who are carriers of significant variants.

Cost analysis of a managed care decentralized outpatient pharmacy anticoagulation service.

PubMed

Anderson, Robert J

2004-01-01

To determine the per-patient-per-month (PPPM) cost of a decentralized outpatient pharmacy anticoagulation service (OPAS) in patients with chronic atrial fibrillation (AF) who were maintained on warfarin sodium therapy in a managed care setting, to compare the annual costs versus the risk for stroke, and to assess the quality of the anticoagulant management. Data were collected retrospectively from clinical, research, and administrative claims databases. Patient demographic data were stratified to include age and risk factors for stroke. Inclusion criteria for the study were adult patients (>18 years) who were maintained on chronic warfarin therapy with a diagnosis of AF (diagnosis code 427.31) and continuously enrolled during calendar year 2000. The cost analysis included the personnel cost of clinical pharmacy specialists, direct and indirect cost of laboratory tests for international normalized ratios (INR), and anticoagulant (warfarin plus bridge therapy with a low molecular weight heparin) drug cost and dispensing fee. The percentage of INR values within or near target was used to evaluate the effectiveness of the service. A total of 97 patients on chronic warfarin therapy for AF were identified for cost analysis. The demographics for these patients included the following: 71% were male, with 32% of the patients over the age of 75 years, and 60% had 1 or more identifiable risk factors for stroke. Utilizing established criteria, 80.4% of the sample was considered to be at high risk for ischemic stroke. A majority of the patients (94.8%) had nonvalvular disease, with an INR goal in the range of 2 to 3 in 91.8% of the cases. The PPPM cost for the OPAS monitoring service was $51.25, distributed as $13.78 (27%) in personnel costs for monitoring pharmacists, $18.38 (36%) for lab tests, and $19.09 (37%) for anticoagulant drug costs. These costs did not significantly differ among patient groups with various risks for ischemic stroke. For nonvalvular AF patients, the

Patient education about anticoagulant medication: is narrative evidence or statistical evidence more effective?

PubMed

Mazor, Kathleen M; Baril, Joann; Dugan, Elizabeth; Spencer, Frederick; Burgwinkle, Pamela; Gurwitz, Jerry H

2007-12-01

To determine the relative impact of incorporating narrative evidence, statistical evidence or both into patient education about warfarin, a widely used oral anticoagulant medication. 600 patients receiving anticoagulant therapy were randomly assigned to view one of three versions of a video depicting a physician-patient encounter where anticoagulation treatment was discussed, or usual care (no video). The videos differed in whether the physician used narrative evidence (patient anecdotes), statistical evidence, or both to highlight key information. 317 patients completed both the baseline and post-test questionnaires. Questions assessed knowledge, beliefs and adherence to medication and laboratory monitoring regimens. All three approaches positively effected patients' warfarin-related knowledge, and beliefs in the importance of lab testing; there was also some indication that viewing a video strengthened belief in the benefits of warfarin. There was some indication that narrative evidence had a greater impact than statistical evidence on beliefs about the importance of lab testing and on knowledge. No other evidence of the differential effectiveness of either approach was found. No statistically significant effect was found on intent to adhere, or documented adherence to lab monitoring. Videos depicting a physician-patient dialogue about warfarin were effective in educating patients about anticoagulant medication, and had a positive impact on their beliefs. The use of narrative evidence in the form of patient anecdotes may be more effective than statistical evidence for some patient outcomes. Patients on oral anticoagulant therapy may benefit from periodic educational efforts reinforcing key medication safety information, even after initial education and ongoing monitoring. Incorporating patient anecdotes into physician-patient dialogues or educational materials may increase the effectiveness of the message.

Contact laser prostatectomy in a patient on chronic anticoagulation

NASA Astrophysics Data System (ADS)

Mueller, Edward J.

1995-05-01

The `gold standard' therapy for patients with symptomatic bladder outlet obstruction secondary to benign prostatic hyperplasia has always been electrocautery TURP. However, in patients with medical problems requiring chronic anticoagulation, this procedure is contraindicated due to the extreme risk of hemorrhage, both during the procedure and the immediate post operative period. With the recent development of contact laser prostatectomy the patient on chronic anticoagulation can safely undergo the procedure. Herein, I present a case of a 60 year old with significant bladder outlet obstruction yielding an AUA symptom score of 18. The patient had a history of multiple episodes of deep venous thrombosis of the left leg with three prior pulmonary emboli. He was maintained on chronic anticoagulation with alternating days of 3.5 mg. and 5.0 mg. of warfarin sodium (coumadin). Preoperative cystoscopy showed a 4 cm prostatic fossa obstructed by tri-lobar hypertrophy, with large kissing lateral lobes and visual obstruction from the verumontanum. The patient underwent a contact laser prostatectomy with the SLT Nd:YAG laser at 50 watts. There was minimal bleeding both during the procedure and in the immediate postoperative period. At three months post-op the AUA symptom score had decreased to 2. This case demonstrated that contact laser prostatectomy can be safely and effectively performed in patients on chronic anticoagulation.

New horizons in anticoagulation: Direct oral anticoagulants and their implications in oral surgery

PubMed Central

Ripollés-de Ramón, Jorge; Collado-Yurrita, Luis; Vaello-Checa, Iris; Colmenero-Ruiz, Constantino; Helm, Alexandra; Ciudad-Cabañas, Maria-José; Serrano-Cuenca, Victoriano

2017-01-01

Background Thrombotic disorders remain a leading cause of death in the Western World. For decades, vitamin K antagonists used in the prevention of this pathology, such as warfarin or sintrom, were the only oral agents available for long-term anticoagulation, in spite of their disadvantages. Material and Methods An electronic database search was carried out on MedLine and The Cochrane Library Plus, without restrictions on the type of study nor dates, in English and Spanish. Abstracts were reviewed, and complete articles if necessary, considering all articles that included recommendations on DOACs and oral surgery. Results In recent years, the so-called “new oral anticoagulants” have been introduced in clinical practice to treat those patients whose medical conditions require long-term anticoagulant treatment, replacing traditional oral anticoagulants. Conclusions The new oral anticoagulants represent new therapeutic options, with a number of advantages such as poor interaction with food, minor drug interactions, and do not require periodic dose adjustments or routine controls. The purpose of this review is to establish an update on the new oral anticoagulants: Dabigatran, Rivarozaban, Apixaban and Edoxaban. Key words:Novel oral anticoagulants, Dabigatran, Rivaroxaban, Apixaban, Edoxaban, bleeding management, oral surgery, Anti-IIa, Anti Xa. PMID:28809374

Rapid bedside coagulometry prior to urgent neurosurgical procedures in anticoagulated patients.

PubMed

Beynon, Christopher; Jakobs, Martin; Rizos, Timolaos; Unterberg, Andreas W; Sakowitz, Oliver W

2014-01-01

With the increased use of oral anticoagulation with vitamin K antagonists, emergency physicians encounter a growing number of patients requiring a rapid reversal of anticoagulant effects in order to perform urgent surgical procedures. Initiation of these procedures can be delayed because the coagulation status has to be assessed through examination of blood samples in central laboratories (CL). This delay may lead to negative effects, especially in potentially life-threatening conditions such as intracranial haemorrhage. Point-of-care (POC) devices for assessment of international normalized ratio (POC INR) have improved the management of anticoagulation therapy in the outpatient setting. The use of these devices may also have beneficial effects in the treatment of anticoagulated patients requiring urgent neurosurgical procedures. The primary aim of this study was to analyse the potential of POC-guided assessment of INR to reduce time to potentially life-saving neurosurgery in this setting. Feasibility and accuracy as well as the gain of time through the use of this device were analysed. The POC coagulometer CoaguChek XS(®) was used in 17 patients with a history of anticoagulant use and a condition requiring urgent anticoagulant reversal prior to neurosurgical procedures (burr-hole trepanation: n = 8, craniotomy: n = 7, laminectomy: n = 2). No technical difficulties occurred and rapid assessment of INR was achieved in all cases within 2 min. POC INR values correlated well with CL INR assessment with a mean INR deviation of 0.036 ± 0.12. The mean gain of time through the use of the POC INR device compared with CL assessment of INR was 47 ± 6 min (range: 37-61 min). Our initial experiences with a POC INR device in anticoagulated patients undergoing urgent neurosurgical procedures demonstrate that its use may contribute to an improved management of these patients.

Trends in initiation of direct oral anticoagulant therapies for atrial fibrillation in a national population-based cross-sectional study in the French health insurance databases

PubMed Central

Huiart, Laetitia; Ferdynus, Cyril; Renoux, Christel; Beaugrand, Amélie; Lafarge, Sophie; Bruneau, Léa; Suissa, Samy; Maillard, Olivier; Ranouil, Xavier

2018-01-01

Objective Unlike several other national health agencies, French health authorities recommended that the newer direct oral anticoagulant (DOAC) agents only be prescribed as second choice for the treatment of newly diagnosed non-valvular atrial fibrillation (NVAF), with vitamin K antagonists (VKA) remaining the first choice. We investigated the patterns of use of DOACs versus VKA in the treatment of NVAF in France over the first 5 years of DOAC availability. We also identified the changes in patient characteristics of those who initiated DOAC treatment over this time period. Methods Based on the French National Health Administrative Database, we constituted a population-based cohort of all patients who were newly treated for NVAF between January 2011 and December 2015. Trends in drug use were described as the percentage of patients initiating each drug at the time of treatment initiation. A multivariate analysis using logistic regression model was performed to identify independent sociodemographic and clinical predictors of initial anticoagulant choice. Results The cohort comprised 814 446 patients who had received a new anticoagulant treatment for NVAF. The proportion of patients using DOACs as initial anticoagulant therapy reached 54% 3 months after the Health Ministry approved the reimbursement of dabigatran for NVAF, and 61% by the end of 2015, versus VKA use. In the multivariate analysis, we found that DOAC initiators were younger and healthier overall than VKA initiators, and this tendency was reinforced over the 2011–2014 period. DOACs were more frequently prescribed by cardiologists in 2012 and after (adjusted OR in 2012: 2.47; 95% CI 2.40 to 2.54). Conclusion Despite recommendations from health authorities, DOACs have been rapidly and massively adopted as initial therapy for NVAF in France. Observational studies should account for the fact that patients selected to initiate DOAC treatment are healthier overall, as failure to do so may bias the risk�

Gastrointestinal bleeding risk of non-vitamin K oral anticoagulants is similar to warfarin - a Japanese retrospective cohort study
.

PubMed

Shirai, Tsuguru; Yamamoto, Takatsugu; Kawasugi, Kazuo; Kuyama, Yasushi; Kita, Hiroto

2016-11-01

Although several non-vitamin K oral anticoagulants have been developed to prevent cardiogenic thrombosis, the status of hemorrhagic complications in the clinical setting among Asian populations, including Japan, remains unclear. We conducted this retrospective cohort study to clarify the current status of hemorrhagic events during antithrombotic therapy with non-vitamin K oral anticoagulants, with particular focus on gastrointestinal bleeding. Medical charts of 475 patients prescribed dabigatran, rivaroxaban, or apixaban between April 2011 and September 2014 were reviewed to examine whether any hemorrhagic events occurred, compared with 135 patients who received warfarin between April 2009 and March 2011. Incidences of total and actionable hemorrhage in patient taking non-vitamin K oral anticoagulants were 13.8% per year and 4.6% per year, respectively, showing no significant differences from those in warfarin users (9.3% per year and 5.0% per year, respectively). In addition, actionable gastrointestinal hemorrhage occurred at similar rates in non-vitamin K oral anticoagulants users (2.1% per year) and warfarin users (1.5% per year). Most hemorrhages were from the lower gastrointestinal tract, and considerable events involved perianal bleeding. Multiple regression analysis showed that age, concomitant dual antiplatelet therapy, and concomitant nonsteroidal anti-inflammatory drug therapy were significant factors related to actionable gastrointestinal bleeding. Risk of gastrointestinal hemorrhage in patients taking non-vitamin K oral anticoagulants was similar to that in patients taking warfarin. The dominant bleeding site was the lower gastrointestinal tract.
.

The use of play therapy in the preparation of children undergoing MR imaging.

PubMed

Pressdee, D; May, L; Eastman, E; Grier, D

1997-12-01

Magnetic resonance (MR) imaging has become an important technique in the evaluation of a wide range of congenital and acquired conditions in children. The ability to image in multiple anatomic planes without the use of ionizing radiation has particular advantages. However scan times can be long, and the narrow bore and noise generated by most units make the procedure very intimidating to the young child. The use of surface coils may exacerbate this, often necessitating recourse to sedation or anaesthesia. We describe a technique involving play therapy which we have found useful in the preparation of young children for MR imaging and which has reduced the number of non-diagnostic scans and the need for sedation or anaesthesia.

[Comparison of quality and hemorragic risk of oral anticoagulant therapy using acenocoumarol versus warfarin].

PubMed

Oliva Berini, Elvira; Galán Alvarez, Pilar; Pacheco Onrubia, Ana María

2008-06-21

Long half life oral anticoagulants have shown a higher anticoagulation stability and a lower hemorragic risk than those of a short half life. We have compared therapeutic stability and hemorragic risk of acenocoumarol versus warfarin in 2 groups of patients on preventive anticoagulation because of atrial fibrilation (international normalised ratio [INR]: 2-3). Data on 120 patients treated with acenocoumarol and 120 on warfarin treatment who had started and continued treatment in our hospital for a minimum of a year was collected. The percentage of visits within the intended range of INR (2 to 3) was 65.5% with warfarin and 63.4% with acenocoumarol. Thirty percent of patients on warfarin had 75% or more of their controls within range, while for those treated with acenocoumarol this percentage was 22.5%. In the acenocoumarol group, 0.3 visits/patient/year presented an INR > or = 6 versus 0.07 in the warfarin group (p = 0.003). Patients treated with acenocoumarol show a higher risk of presenting with an INR > or = 6, but no statistically significant differences are observed in therapeutic stability.

Dual antiplatelet therapy after percutaneous coronary intervention with stent implantation in patients taking chronic oral anticoagulation.

PubMed

Rogacka, Renata; Chieffo, Alaide; Michev, Iassen; Airoldi, Flavio; Latib, Azeem; Cosgrave, John; Montorfano, Matteo; Carlino, Mauro; Sangiorgi, Giuseppe M; Castelli, Alfredo; Godino, Cosmo; Magni, Valeria; Aranzulla, Tiziana C; Romagnoli, Enrico; Colombo, Antonio

2008-02-01

The purpose of this study was to evaluate the safety of dual antiplatelet therapy in patients in whom long-term anticoagulation (AC) with warfarin is recommended. The optimal antithrombotic strategy after percutaneous coronary intervention (PCI) for patients receiving AC is unclear. Consecutive patients who underwent stent implantation and were discharged on triple therapy (defined as the combination of aspirin and thienopyridines and AC) were analyzed. Of the 127 patients with 224 lesions, 86.6% were men, with a mean age of 69.9 +/- 8.8 years. Drug-eluting stents (DES) were positioned in 71 (55.9%), and bare-metal stents (BMS) were positioned in 56 (44.1%) patients. Atrial fibrillation (AF) was the main indication (59.1%) for AC treatment. The mean triple therapy duration was 5.6 +/- 4.6 months, and clinical follow-up was 21.0 +/- 19.8 months. During the triple therapy period, 6 patients (4.7%) developed major bleeding complications; 67% occurred within the first month. No significant differences between DES and BMS were observed in the incidence of major (5.6% vs. 3.6%, respectively, p = 1.0) and minor (1.4% vs. 3.6%, respectively, p = 0.57) bleeding and mortality (5.6% vs. 1.8%, respectively, p = 0.39). A significant difference was observed in favor of DES in target vessel revascularization (14.1% vs. 26.8%, p = 0.041). While receiving triple therapy, major bleeding occurred in 4.7% of patients; one-half of the events were lethal, and most occurred within the first month.

Acute Pulmonary Embolism in Emergency Department Patients Despite Therapeutic Anticoagulation

PubMed Central

Liu, Michelle Y.; Ballard, Dustin W.; Huang, Jie; Rauchwerger, Adina S.; Reed, Mary E.; Bouvet, Sean C.

2018-01-01

cava filters. Thirty-day outcomes included one major hemorrhage and one additional death. No patients experienced recurrent or worsening VTE. Conclusion We found a low prevalence of therapeutic anticoagulation at the time of acute PE diagnosis. Most patients with breakthrough PE underwent a change in therapy, though management varied widely. Subtherapeutic anticoagulation levels in the preceding weeks were common and support the importance of anticoagulation adherence. PMID:29760849

External Beam Radiotherapy for Prostate Cancer Patients on Anticoagulation Therapy: How Significant is the Bleeding Toxicity?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choe, Kevin S.; Jani, Ashesh B.; Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.ed

Purpose: To characterize the bleeding toxicity associated with external beam radiotherapy for prostate cancer patients receiving anticoagulation (AC) therapy. Methods and Materials: The study cohort consisted of 568 patients with adenocarcinoma of the prostate who were treated with definitive external beam radiotherapy. Of these men, 79 were receiving AC therapy with either warfarin or clopidogrel. All patients were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Bleeding complications were recorded during treatment and subsequent follow-up visits. Results: With a median follow-up of 48 months, the 4-year actuarial risk of Grade 3 or worse bleeding toxicity was 15.5% for those receivingmore » AC therapy compared with 3.6% among those not receiving AC (p < .0001). On multivariate analysis, AC therapy was the only significant factor associated with Grade 3 or worse bleeding (p < .0001). For patients taking AC therapy, the crude rate of bleeding was 39.2%. Multivariate analysis within the AC group demonstrated that a higher radiotherapy dose (p = .0408), intensity-modulated radiotherapy (p = 0.0136), and previous transurethral resection of the prostate (p = .0001) were associated with Grade 2 or worse bleeding toxicity. Androgen deprivation therapy was protective against bleeding, with borderline significance (p = 0.0599). Dose-volume histogram analysis revealed that Grade 3 or worse bleeding was minimized if the percentage of the rectum receiving >=70 Gy was <10% or the rectum receiving >=50 Gy was <50%. Conclusion: Patients taking AC therapy have a substantial risk of bleeding toxicity from external beam radiotherapy. In this setting, dose escalation or intensity-modulated radiotherapy should be used judiciously. With adherence to strict dose-volume histogram criteria and minimizing hotspots, the risk of severe bleeding might be reduced.« less

Direct oral anticoagulants: An update.

PubMed

Franco Moreno, Ana Isabel; Martín Díaz, Rosa María; García Navarro, María José

2017-12-30

Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Recurrence of ICH after resumption of anticoagulation with VK antagonists: CHIRONE study.

PubMed

Poli, Daniela; Antonucci, Emilia; Dentali, Francesco; Erba, Nicoletta; Testa, Sophie; Tiraferri, Eros; Palareti, Gualtiero

2014-03-25

To evaluate the risk of recurrent intracranial hemorrhage (ICH) in patients on vitamin K antagonists (VKAs) after a first episode of ICH. The Cerebral Haemorrhage in patients Restarting Oral Anticoagulant Therapy (CHIRONE) Study collected data of patients eligible for the study from the database of 27 centers affiliated with the Italian Federation of Anticoagulation Clinics. We enrolled 267 patients (163 male, median age 73.9 years) who had received VKA anticoagulation after an ICH event. During the total period of follow-up (778 patient-years), ICH recurred in 20 patients (7.5%; rate 2.56 × 100 patient-years) at a median time of 16.5 months, and was fatal in 5 patients (25%; rate 0.4 × 100 patient-years). Male sex, hypertension, prosthetic valves, previous ischemic stroke, renal failure, cancer, and spontaneous events were associated with the risk of recurrence, though none of them in isolation reached statistical significance. More than one-third of spontaneous recurrences occurred in patients with a posttraumatic index event. Our results show that patients with a history of ICH carry a significant risk of recurrent ICH when treated with VKA anticoagulation. The risk is also present, though to a lower degree, in patients with previous posttraumatic events. All patients with a history of ICH require a careful evaluation of their thromboembolic risk to estimate the net clinical benefit of (re)starting anticoagulation with VKAs.

Zero TE-based pseudo-CT image conversion in the head and its application in PET/MR attenuation correction and MR-guided radiation therapy planning.

PubMed

Wiesinger, Florian; Bylund, Mikael; Yang, Jaewon; Kaushik, Sandeep; Shanbhag, Dattesh; Ahn, Sangtae; Jonsson, Joakim H; Lundman, Josef A; Hope, Thomas; Nyholm, Tufve; Larson, Peder; Cozzini, Cristina

2018-02-18

To describe a method for converting Zero TE (ZTE) MR images into X-ray attenuation information in the form of pseudo-CT images and demonstrate its performance for (1) attenuation correction (AC) in PET/MR and (2) dose planning in MR-guided radiation therapy planning (RTP). Proton density-weighted ZTE images were acquired as input for MR-based pseudo-CT conversion, providing (1) efficient capture of short-lived bone signals, (2) flat soft-tissue contrast, and (3) fast and robust 3D MR imaging. After bias correction and normalization, the images were segmented into bone, soft-tissue, and air by means of thresholding and morphological refinements. Fixed Hounsfield replacement values were assigned for air (-1000 HU) and soft-tissue (+42 HU), whereas continuous linear mapping was used for bone. The obtained ZTE-derived pseudo-CT images accurately resembled the true CT images (i.e., Dice coefficient for bone overlap of 0.73 ± 0.08 and mean absolute error of 123 ± 25 HU evaluated over the whole head, including errors from residual registration mismatches in the neck and mouth regions). The linear bone mapping accounted for bone density variations. Averaged across five patients, ZTE-based AC demonstrated a PET error of -0.04 ± 1.68% relative to CT-based AC. Similarly, for RTP assessed in eight patients, the absolute dose difference over the target volume was found to be 0.23 ± 0.42%. The described method enables MR to pseudo-CT image conversion for the head in an accurate, robust, and fast manner without relying on anatomical prior knowledge. Potential applications include PET/MR-AC, and MR-guided RTP. © 2018 International Society for Magnetic Resonance in Medicine.

[Retrospective analysis of correlative factors between digestive system injury and anticoagulant or antiplatelet-agents].

PubMed

Cui, Ning; Luo, Hesheng

2014-05-27

To explore the correlative factors and clinical characteristics of digestive system injury during the treatment of anticoagulant and (or) antiplatelet-agents. A total of 1 443 hospitalized patients on anticoagulant and (or) antiplatelet-agents from January 2010 to December 2013 at Renmin Hospital of Wuhan University were analyzed retrospectively. Their length of hospital stay was from 5 to 27 days. Most of them were elderly males (n = 880, 61.0%) with an average age of (62 ± 6) years. 1 138 patients (78.9%) were farmers, workers or someone without a specific occupation. During the treatment of anticoagulant/antiplatelet-agents, statistical difference existed (P = 0.01) between positively and negatively previous digestive disease groups for actively newly occurring digestive system injury (16.0% (41/256) vs 15.9% (189/1 187)). After the dosing of anticoagulant and (or) antiplatelet-agents, 57 (66.3%, 57/86) patients were complicated by hemorrhage of digestive tract, taking 62.9% (61/97) of all positive result patients for Helicobacter pylori test. Comparing preventive PPI group with no PPI group, there was no marked statistical differences (P = 2.67) for digestive system complication (including hemorrhage of digestive tract) while receiving anticoagulant and (or) antiplatelet-agents (13.9% (74/533) vs 17.1% (156/910)). During anticoagulant and/or antiplatelet-agent therapy, 185 patients (12.8%) were complicated by peptic ulcer or peptic ulcer with bleeding, 40 patients (2.8%) had erosive gastritis and 5 (0.3%) developed acute gastric mucosal lesions. And 42 of 76 patients complicated by hemorrhage of digestive tract underwent endoscopic hemostasis while 2 patients were operated. Ninety-seven patients (6.7%) died, including 61 (62.9%, 61/97) from hemorrhage of digestive tract. The remainder became cured, improved and discharged. Moreover, no significant statistical differences existed (P = 2.29) among three combination group (aspirin, clopidogrel, warfarin), two

Discrepancies between Patients' Preferences and Educational Programs on Oral Anticoagulant Therapy: A Survey in Community Pharmacies and Hospital Consultations.

PubMed

Macquart de Terline, Diane; Hejblum, Gilles; Fernandez, Christine; Cohen, Ariel; Antignac, Marie

2016-01-01

Oral anticoagulation therapy is increasingly used for the prevention and treatment of thromboembolic complications in various clinical situations. Nowadays, education programs for patients treated with anticoagulants constitute an integrated component of their management. However, such programs are usually based on the healthcare providers' perceptions of what patients should know, rather than on patients' preferences. To investigate patients' viewpoints on educational needs and preferred modalities of information delivery. We conducted an observational study based on a self-administered questionnaire. To explore several profiles of patients, the study was designed for enrolling patients in two settings: during outpatient consultations in a cardiology department (Saint Antoine Hospital, Paris, France) and in community pharmacies throughout France. Of the 371 patients who completed the questionnaire, 187 (50.4%) were recruited during an outpatient consultation and 184 (49.6%) were recruited in community pharmacies. 84.1% of patients were receiving a vitamin K antagonist and 15.6% a direct oral anticoagulant. Patients ranked 16 of 21 (76.2%) questionnaire items on information about their treatment as important or essential; information on adverse effects of treatment was the highest ranked domain (mean score 2.38, 95% CI 2.30-2.46). Pharmacists (1.69, 1.58-1.80), nurses (1.05, 0.95-1.16), and patient associations (0.36, 0.29-0.44), along with group sessions (0.85, 0.75-0.95), the internet (0.77, 0.67-0.88), and delivery of material at the patient's home (1.26, 1.14-1.38), were ranked poorly in terms of delivering educational material. This study revealed substantial discrepancies between patient preferences and current educational programs. These findings should be useful for tailoring future educational programs that are better adapted to patients, with a potential associated enhancement of their effectiveness.

Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: an exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials.

PubMed

Flaker, Greg C; Gruber, Michael; Connolly, Stuart J; Goldman, Steven; Chaparro, Sandra; Vahanian, Alec; Halinen, Matti O; Horrow, Jay; Halperin, Jonathan L

2006-11-01

Aspirin is used in combination with anticoagulant therapy in patients with atrial fibrillation (AF), but evidence of additional efficacy is not available. We compared ischemic events and bleeding in the SPORTIF III and IV randomized trials of anticoagulation with warfarin (international normalized ratio 2-3) or fixed-dose ximelagatran. Low-dose aspirin (<100 mg/d) was allowed based on prevailing guidelines. The 14% of patients receiving aspirin more often had diabetes (27.5% vs 23%, P < .01), coronary artery disease (69% vs 41%, P < .01), previous stroke or transient ischemic attack (26% vs 20%, P < .01), and left ventricular dysfunction (41% vs 36%, P < .01). Addition of aspirin to either warfarin or ximelagatran was associated with no reduction in stroke or systemic embolism. Major bleeding occurred significantly more often with aspirin plus warfarin (3.9% per year) than with warfarin alone (2.3% per year, P < .01), aspirin plus ximelagatran (2.0% per year), or ximelagatran alone (1.9% per year). The rate of myocardial infarction with aspirin and warfarin (0.6% per year) was not significantly different from that with ximelagatran alone (1.0% per year), warfarin alone (1.0% per year), or aspirin and ximelagatran (1.4% per year). Aspirin combined with anticoagulant therapy was associated with no reduction in stroke, systemic embolism, or myocardial infarction in patients with AF. Aspirin combined with warfarin was associated with an incremental rate of major bleeding of 1.6% per year. No increased major bleeding occurred with aspirin and ximelagatran. These results suggest that the risks associated with addition of aspirin to anticoagulation in patients with AF outweigh the benefit.

MR-Guided Prostate Interventions

PubMed Central

Tempany, Clare; Straus, Sarah; Hata, Nobuhiko; Haker, Steven

2009-01-01

In this article the current issues of diagnosis and detection of prostate cancer are reviewed. The limitations for current techniques are highlighted and some possible solutions with MR imaging and MR-guided biopsy approaches are reviewed. There are several different biopsy approaches under investigation. These include transperineal open magnet approaches to closed-bore 1.5T transrectal biopsies. The imaging, image processing, and tracking methods are also discussed. In the arena of therapy, MR guidance has been used in conjunction with radiation methods, either brachytherapy or external delivery. The principles of the radiation treatment, the toxicities, and use of images are outlined. The future role of imaging and image-guided interventions lie with providing a noninvasive surrogate for cancer surveillance or monitoring treatment response. The shift to minimally invasive focal therapies has already begun and will be very exciting when MR-guided focused ultrasound surgery reaches its full potential. PMID:18219689

Response to warfarin and other oral anticoagulants: effects of disease states.

PubMed

Demirkan, K; Stephens, M A; Newman, K P; Self, T H

2000-05-01

Warfarin is associated with numerous drug and food interactions, and much attention has been appropriately focused on this subject. Because several disease states may also affect response to oral anticoagulants, we present a summary of the literature. We searched MEDLINE for original articles on the effect of disease states on response to warfarin. Liver disease and thyroid dysfunction are well-documented as affecting warfarin response. Further study is needed to establish whether febrile illness, congestive heart failure, and other disease states enhance the effect of warfarin in some patients. Careful monitoring of anticoagulant therapy in patients with diseases that have the potential to affect warfarin response could increase safety and efficacy of this important agent.

Impact of self-funding on patient experience of oral anticoagulation self-monitoring: a qualitative study

PubMed Central

Tompson, Alice; Heneghan, Carl; Sutton, Stephen; Fitzmaurice, David; Ward, Alison

2016-01-01

Objective To explore the impact self-funding has on patient experience of oral anticoagulation therapy self-monitoring. Design Semistructured, qualitative interviews were conducted. Transcripts were analysed thematically using constant comparison. Setting England. Participants Interviewees were participants of the Cohort Study of Anticoagulation Self-Monitoring (CASM). Cohort members were recruited as they bought a monitor from the major manufacturer in the UK. A purposive sample was invited to be interviewed on completion of the 12-month cohort follow-up. Data Patient narratives on their experiences of self-monitoring their oral anticoagulation therapy in non-trial conditions. Results 26 interviews were completed. Interviewees viewed purchasing the monitoring device as a long-term commitment balancing the limitations of clinic-based monitoring against the cost. They were unable to try out the monitor prior to purchase and therefore had to be confident in their own ability to use it. The variable provision of self-monitoring equipment caused resentment, and interviewees were uncomfortable negotiating with healthcare professionals. High test strip usage while learning how to use the monitor caused anxiety that was exacerbated by worries about their cost. However, self-funding did mean that interviewees felt a sense of ownership and were determined to persevere to overcome problems. Conclusions Self-funding has negative implications in terms of equity of access; however, the money invested acts as a barrier to discontinuation. If oral anticoagulation therapy self-monitoring devices and consumables were provided free of charge in routine care, the training and support available in England may need to be reviewed to prevent discontinuation rates rising to those observed in clinical trials. PMID:28011812

Effects of pelletized anticoagulant rodenticides on California quail

USGS Publications Warehouse

Blus, L.J.; Henny, C.J.; Grove, R.A.

1985-01-01

A moribund, emaciated California quail (Callipepla californica) that was found in an orchard in the state of Washington had an impacted crop and gizzard. Pellets containing the anticoagulant chlorophacinone (Rozol, RO) were in the crop; the gizzard contents consisted of a pink mass of paraffin that was selectively accumulated from the paraffinized pellets. The plasma prothrombin time of 28 sec was near that determined for control quail. The signs of RO intoxication seen in the moribund wild quail were duplicated in captive quail given ad libitum diets of either RO or another paraffinized chlorophacinone pellet (Mr. Rat Guard II, MRG). This left little doubt that paraffin impaction of the gizzard was the primary problem. All captive quail fed RO or MRG pellets showed no increases in prothrombin times compared to control values, died in an emaciated condition, and had gizzards impacted with paraffin.

Physical activity and risk of bleeding in elderly patients taking anticoagulants.

PubMed

Frey, P M; Méan, M; Limacher, A; Jaeger, K; Beer, H-J; Frauchiger, B; Aschwanden, M; Rodondi, N; Righini, M; Egloff, M; Osterwalder, J; Kucher, N; Angelillo-Scherrer, A; Husmann, M; Banyai, M; Matter, C M; Aujesky, D

2015-02-01

Although the possibility of bleeding during anticoagulant treatment may limit patients from taking part in physical activity, the association between physical activity and anticoagulation-related bleeding is uncertain. To determine whether physical activity is associated with bleeding in elderly patients taking anticoagulants. In a prospective multicenter cohort study of 988 patients aged ≥ 65 years receiving anticoagulants for venous thromboembolism, we assessed patients' self-reported physical activity level. The primary outcome was the time to a first major bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin or leading to transfusions. The secondary outcome was the time to a first clinically relevant non-major bleeding. We examined the association between physical activity level and time to a first bleeding by using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. During a mean follow-up of 22 months, patients with a low, moderate, and high physical activity level had an incidence of major bleeding of 11.6, 6.3, and 3.1 events per 100 patient-years and an incidence of clinically relevant non-major bleeding of 14.0, 10.3, and 7.7 events per 100 patient-years, respectively. A high physical activity level was significantly associated with a lower risk of major bleeding (adjusted sub-hazard ratio 0.40, 95% confidence interval 0.22-0.72). There was no association between physical activity and non-major bleeding. A high level of physical activity is associated with a decreased risk of major bleeding in elderly patients receiving anticoagulant therapy. © 2014 International Society on Thrombosis and Haemostasis.

Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring?

PubMed

Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla

2014-10-01

The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo. Thieme Medical Publishers

POST-NOAC: Portuguese observational study of intracranial hemorrhage on non-vitamin K antagonist oral anticoagulants.

PubMed

Marques-Matos, Cláudia; Alves, José Nuno; Marto, João Pedro; Ribeiro, Joana Afonso; Monteiro, Ana; Araújo, José; Silva, Fernando; Grenho, Fátima; Viana-Baptista, Miguel; Sargento-Freitas, João; Pinho, João; Azevedo, Elsa

2017-08-01

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA 2 DS 2 VASc, HAS-BLED, and anticoagulation reversal revealed that non-vitamin K antagonist oral anticoagulants did not influence three-month mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.39-1.80, p = 0.638). Multivariable ordinal regression for three-month functional outcome did not show a significant shift of modified Rankin Scale scores in non-vitamin K antagonist oral anticoagulants patients (odds ratio (OR) 1.26, 95%CI 0.55-2.87, p = 0.585). Conclusions We detected no significant differences in the three-month outcome between non-vitamin K antagonist oral anticoagulants

MR-guided prostate interventions.

PubMed

Tempany, Clare; Straus, Sarah; Hata, Nobuhiko; Haker, Steven

2008-02-01

In this article the current issues of diagnosis and detection of prostate cancer are reviewed. The limitations for current techniques are highlighted and some possible solutions with MR imaging and MR-guided biopsy approaches are reviewed. There are several different biopsy approaches under investigation. These include transperineal open magnet approaches to closed-bore 1.5T transrectal biopsies. The imaging, image processing, and tracking methods are also discussed. In the arena of therapy, MR guidance has been used in conjunction with radiation methods, either brachytherapy or external delivery. The principles of the radiation treatment, the toxicities, and use of images are outlined. The future role of imaging and image-guided interventions lie with providing a noninvasive surrogate for cancer surveillance or monitoring treatment response. The shift to minimally invasive focal therapies has already begun and will be very exciting when MR-guided focused ultrasound surgery reaches its full potential. (Copyright) 2008 Wiley-Liss, Inc.

Restarting Anticoagulant Treatment After Intracranial Hemorrhage in Patients With Atrial Fibrillation and the Impact on Recurrent Stroke, Mortality, and Bleeding: A Nationwide Cohort Study.

PubMed

Nielsen, Peter Brønnum; Larsen, Torben Bjerregaard; Skjøth, Flemming; Gorst-Rasmussen, Anders; Rasmussen, Lars Hvilsted; Lip, Gregory Y H

2015-08-11

Intracranial hemorrhage is the most feared complication of oral anticoagulant treatment. The optimal treatment option for patients with atrial fibrillation who survive an intracranial hemorrhage remains unknown. We hypothesized that restarting oral anticoagulant treatment was associated with a lower risk of stroke and mortality in comparison with not restarting. Linkage of 3 Danish nationwide registries in the period between 1997 and 2013 identified patients with atrial fibrillation on oral anticoagulant treatment with incident intracranial hemorrhage. Patients were stratified by treatment regimens (no treatment, oral anticoagulant treatment, or antiplatelet therapy) after the intracranial hemorrhage. Event rates were assessed 6 weeks after hospital discharge and compared with Cox proportional hazard models. In 1752 patients (1 year of follow-up), the rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for patients treated with oral anticoagulants was 13.6, in comparison with 27.3 for nontreated patients and 25.7 for patients receiving antiplatelet therapy. The rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for recurrent intracranial hemorrhage, the rate of ischemic stroke/systemic embolism, and all-cause mortality (per 100 person-years) patients treated with oral anticoagulants was 8.0, in comparison with 8.6 for nontreated patients and 5.3 for patients receiving antiplatelet therapy. The adjusted hazard ratio of ischemic stroke/systemic embolism and all-cause mortality was 0.55 (95% confidence interval, 0.39-0.78) in patients on oral anticoagulant treatment in comparison with no treatment. For ischemic stroke/systemic embolism and for all-cause mortality, hazard ratios were 0.59 (95% confidence interval, 0.33-1.03) and 0.55 (95% confidence interval, 0.37-0.82), respectively. Oral anticoagulant treatment was associated with a significant reduction in ischemic stroke/all-cause mortality

Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines.

PubMed

Veitch, Andrew M; Vanbiervliet, Geoffroy; Gershlick, Anthony H; Boustiere, Christian; Baglin, Trevor P; Smith, Lesley-Ann; Radaelli, Franco; Knight, Evelyn; Gralnek, Ian M; Hassan, Cesare; Dumonceau, Jean-Marc

2016-04-01

The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage vs. thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor): For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation);For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation).For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). Warfarin: The advice for warfarin is fundamentally unchanged from BSG 2008 guidance. Direct Oral Anticoagulants (DOAC): For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation). For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken ≥ 48 hours before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30 - 50 mL/min we recommend that the last dose of DOAC be taken 72 hours before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation). © Georg Thieme Verlag KG Stuttgart · New York.

The Feasibility of Conformal Thermal Therapy with Transurethral Ultrasound Heating Applicators and MR Temperature Feedback

NASA Astrophysics Data System (ADS)

Choy, Vanessa; Tang, Kee; Wachsmuth, Jeff; Chopra, Rajiv; Bronskill, Michael

2006-05-01

Transurethral thermal therapy offers a minimally invasive alternative for the treatment of prostate diseases including benign prostate hyperplasia (BPH) and prostate cancer. Accurate heating of a targeted region of the gland can be achieved through the use of a rotating directional heating source incorporating planar ultrasound transducers, and the implementation of active temperature feedback along the beam direction during heating provided by magnetic resonance (MR) thermometry. The performance of this control method with practical spatial, temporal, and temperature resolution (such as angular alignment, spatial resolution, update rate for temperature feedback (imaging time), and the presence of noise) for thermal feedback using a clinical 1.5 T MR scanner was investigated in simulations. As expected, the control algorithm was most sensitive to the presence of noise, with noticeable degradation in its performance above ±2°C of temperature uncertainty. With respect to temporal resolution, acceptable performance was achieved at update rates of 5s or faster. The control algorithm was relatively insensitive to reduced spatial resolution due to the broad nature of the heating pattern produced by the heating applicator, this provides an opportunity to improve signal-to-noise ratio (SNR). The overall simulation results confirm that existing clinical 1.5T MR imagers are capable of providing adequate temperature feedback for transurethral thermal therapy without special pulse sequences or enhanced imaging hardware.

Anticoagulant Medicine: Potential for Drug-Food Interactions

MedlinePlus

... Medications Anticoagulants and Drug-Food Interactions Anticoagulants and Drug-Food Interactions Make an Appointment Ask a Question ... care provider before making the change. Anticoagulants and Medicine There are many medicines that can interact with ...

Kalman filtered MR temperature imaging for laser induced thermal therapies.

PubMed

Fuentes, D; Yung, J; Hazle, J D; Weinberg, J S; Stafford, R J

2012-04-01

The feasibility of using a stochastic form of Pennes bioheat model within a 3-D finite element based Kalman filter (KF) algorithm is critically evaluated for the ability to provide temperature field estimates in the event of magnetic resonance temperature imaging (MRTI) data loss during laser induced thermal therapy (LITT). The ability to recover missing MRTI data was analyzed by systematically removing spatiotemporal information from a clinical MR-guided LITT procedure in human brain and comparing predictions in these regions to the original measurements. Performance was quantitatively evaluated in terms of a dimensionless L(2) (RMS) norm of the temperature error weighted by acquisition uncertainty. During periods of no data corruption, observed error histories demonstrate that the Kalman algorithm does not alter the high quality temperature measurement provided by MR thermal imaging. The KF-MRTI implementation considered is seen to predict the bioheat transfer with RMS error < 4 for a short period of time, ∆t < 10 s, until the data corruption subsides. In its present form, the KF-MRTI method currently fails to compensate for consecutive for consecutive time periods of data loss ∆t > 10 sec.

Kalman Filtered MR Temperature Imaging for Laser Induced Thermal Therapies

PubMed Central

Fuentes, D.; Yung, J.; Hazle, J. D.; Weinberg, J. S.; Stafford, R. J.

2013-01-01

The feasibility of using a stochastic form of Pennes bioheat model within a 3D finite element based Kalman filter (KF) algorithm is critically evaluated for the ability to provide temperature field estimates in the event of magnetic resonance temperature imaging (MRTI) data loss during laser induced thermal therapy (LITT). The ability to recover missing MRTI data was analyzed by systematically removing spatiotemporal information from a clinical MR-guided LITT procedure in human brain and comparing predictions in these regions to the original measurements. Performance was quantitatively evaluated in terms of a dimensionless L2 (RMS) norm of the temperature error weighted by acquisition uncertainty. During periods of no data corruption, observed error histories demonstrate that the Kalman algorithm does not alter the high quality temperature measurement provided by MR thermal imaging. The KF-MRTI implementation considered is seen to predict the bioheat transfer with RMS error < 4 for a short period of time, Δt < 10sec, until the data corruption subsides. In its present form, the KF-MRTI method currently fails to compensate for consecutive for consecutive time periods of data loss Δt > 10sec. PMID:22203706

Acute management of stroke patients taking non-vitamin K antagonist oral anticoagulants Addressing Real-world Anticoagulant Management Issues in Stroke (ARAMIS) Registry: Design and rationale.

PubMed

Xian, Ying; Hernandez, Adrian F; Harding, Tina; Fonarow, Gregg C; Bhatt, Deepak L; Suter, Robert E; Khan, Yosef; Schwamm, Lee H; Peterson, Eric D

2016-12-01

Non-vitamin K antagonist oral anticoagulants (NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban) have been increasingly used as alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation. Yet there is substantial lack of information on how patients on NOACs are currently treated when they have an acute ischemic stroke and the best strategies for treating intracerebral hemorrhage for those on chronic anticoagulation with warfarin or a NOAC. These are critical unmet needs for real world clinical decision making in these emergent patients. The ARAMIS Registry is a multicenter cohort study of acute stroke patients who were taking chronic anticoagulation therapy prior to admission and are admitted with either an acute ischemic stroke or intracerebral hemorrhage. Built upon the existing infrastructure of American Heart Association/American Stroke Association Get With the Guidelines Stroke, the ARAMIS Registry will enroll a total of approximately 10,000 patients (5000 with acute ischemic stroke who are taking a NOAC and 5000 with anticoagulation-related intracerebral hemorrhage who are on warfarin or a NOAC). The primary goals of the ARAMIS Registry are to provide a comprehensive picture of current treatment patterns and outcomes of acute ischemic stroke patients on NOACs, as well as anticoagulation-related intracerebral hemorrhage in patients on either warfarin or NOACs. Beyond characterizing the index hospitalization, up to 2500 patients (1250 ischemic stroke and 1250 intracerebral hemorrhage) who survive to discharge will be enrolled in an optional follow-up sub-study and interviewed at 3 and 6 months after discharge to assess longitudinal medication use, downstream care, functional status, and patient-reported outcomes. The ARAMIS Registry will document the current state of management of NOAC treated patients with acute ischemic stroke as well as contemporary care and outcome of anticoagulation-related intracerebral hemorrhage. These

Pediatric Sarcomas Are Targetable by MR-Guided High Intensity Focused Ultrasound (MR-HIFU): Anatomical Distribution and Radiological Characteristics.

PubMed

Shim, Jenny; Staruch, Robert M; Koral, Korgun; Xie, Xian-Jin; Chopra, Rajiv; Laetsch, Theodore W

2016-10-01

Despite intensive therapy, children with metastatic and recurrent sarcoma or neuroblastoma have a poor prognosis. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is a noninvasive technique allowing the delivery of targeted ultrasound energy under MR imaging guidance. MR-HIFU may be used to ablate tumors without ionizing radiation or target chemotherapy using hyperthermia. Here, we evaluated the anatomic locations of tumors to assess the technical feasibility of MR-HIFU therapy for children with solid tumors. Patients with sarcoma or neuroblastoma with available cross-sectional imaging were studied. Tumors were classified based on the location and surrounding structures within the ultrasound beam path as (i) not targetable, (ii) completely or partially targetable with the currently available MR-HIFU system, and (iii) potentially targetable if a respiratory motion compensation technique was used. Of the 121 patients with sarcoma and 61 patients with neuroblastoma, 64% and 25% of primary tumors were targetable at diagnosis, respectively. Less than 20% of metastases at diagnosis or relapse were targetable for both sarcoma and neuroblastoma. Most targetable lesions were located in extremities or in the pelvis. Respiratory motion compensation may increase the percentage of targetable tumors by 4% for sarcomas and 10% for neuroblastoma. Many pediatric sarcomas are localized at diagnosis and are targetable by current MR-HIFU technology. Some children with neuroblastoma have bony tumors targetable by MR-HIFU at relapse, but few newly diagnosed children with neuroblastoma have tumors amenable to MR-HIFU therapy. Clinical trials of MR-HIFU should focus on patients with anatomically targetable tumors. © 2016 Wiley Periodicals, Inc.

Cancer cell membrane-coated magnetic nanoparticles for MR/NIR fluorescence dual-modal imaging and photodynamic therapy.

PubMed

Li, Jiong; Wang, Xuandong; Zheng, Dongye; Lin, Xinyi; Wei, Zuwu; Zhang, Da; Li, Zhuanfang; Zhang, Yun; Wu, Ming; Liu, Xiaolong

2018-05-22

Theranostic nanoprobes integrated with dual-modal imaging and therapeutic functions, such as photodynamic therapy (PDT), have exhibited significant potency in cancer treatments due to their high imaging accuracy and non-invasive advantages for cancer elimination. However, biocompatibility and highly efficient accumulation of these nanoprobes in tumor are still unsatisfactory for clinical application. In this study, a photosensitizer -loaded magnetic nanobead with surface further coated with a layer of cancer cell membrane (SSAP-Ce6@CCM) was designed to improve the biocompatibility and cellular uptake and ultimately achieve enhanced MR/NIR fluorescence imaging and PDT efficacy. Compared with similar nanobeads without CCM coating, SSAP-Ce6@CCM showed significantly enhanced cellular uptake, as evidenced by Prussian blue staining, confocal laser scanning microscopy (CLSM) and flow cytometric analysis. Consequently, SSAP-Ce6@CCM displayed a more distinct MR/NIR imaging ability and more obvious photo-cytotoxicity towards cancer cells under 670 nm laser irradiation. Furthermore, the enhanced PDT effect benefited from the surface coating of cancer cell membrane was demonstrated in SMMC-7721 tumor-bearing mice through tumor growth observation and tumor tissue pathological examination. Therefore, this CCM-disguised nanobead that integrated the abilities of MR/NIR fluorescence dual-modal imaging and photodynamic therapy might be a promising theranostic platform for tumor treatment.

Anticoagulation Control in Patients With Nonvalvular Atrial Fibrillation Attended at Primary Care Centers in Spain: The PAULA Study.

PubMed

Barrios, Vivencio; Escobar, Carlos; Prieto, Luis; Osorio, Genoveva; Polo, José; Lobos, José María; Vargas, Diego; García, Nicolás

2015-09-01

To determine the current status of anticoagulation control in patients with nonvalvular atrial fibrillation treated with vitamin K antagonists in the primary care setting in Spain. The PAULA study was a multicenter cross-sectional/retrospective observational study conducted throughout Spain. The study included patients with nonvalvular atrial fibrillation who had been receiving vitamin K antagonist therapy during the past year and were attended at primary care centers. International normalized ratio (INR) values over the past 12 months were recorded. The degree of anticoagulation control was defined as the time the patient had remained within the therapeutic range and was determined by both the direct method (poor control < 60%) and by the Rosendaal method (poor control < 65%). The study assessed 1524 patients (mean age, 77.4 ± 8.7 years; 48.6% women; 64.2% in permanent atrial fibrillation; CHADS2 mean, 2.3 ± 1.2; CHA2DS2-VASc, 3.9 ± 1.5, and HAS-BLED, 1.6 ± 0.9). The mean number of INR readings recorded per patient was 14.4 ± 3.8. A total of 56.9% of patients had adequate INR control according to the direct method and 60.6% according to the Rosendaal method. The multivariate analysis identified the following predictors for poor INR control: female sex, dietary habits potentially affecting anticoagulation with vitamin K antagonists, multidrug therapy, and a history of labile INR. Approximately 40% of patients (43.1% by the direct method and 39.4% by the Rosendaal method) with nonvalvular atrial fibrillation who were receiving anticoagulation therapy with vitamin K antagonists in primary care in Spain had poor anticoagulation control during the previous 12 months. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Dual Antithrombotic Therapy with Clopidogrel and Novel Oral Anticoagulants in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Real-world Study.

PubMed

Kebernik, Julia; Borlich, Martin; Tölg, Ralph; El-Mawardy, Mohamed; Abdel-Wahab, Mohamed; Richardt, Gert

2018-06-01

For patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), proper antithrombotic therapy is equivocal. Current guidelines recommend triple therapy, which carries a high risk of bleeding. Recent large trials suggest that dual therapy (DT) with novel oral anticoagulant (NOAC) plus P2Y 12 inhibitor can be an appropriate alternative, but real-world data for this alternative are scarce and the optimal duration of DT has not yet been established. This analysis was performed in a single-center prospective cohort. We investigated 216 PCI patients with indication for anticoagulation due to AF. After PCI patients received DT with reduced doses NOAC plus P2Y 12 inhibitor for 6 months, which was followed by standard dose NOAC monotherapy. Efficacy endpoints were defined as cardiac death, myocardial infarction (MI), stent thrombosis (ST), and stroke. Safety endpoints were bleeding events as defined by Bleeding Academic Consortium (BARC). Baseline characteristics of our study population were described by a CHA 2 DS 2 -VASc score of greater than 4 and a HAS-BLED score of greater than 3. After a mean follow-up of 18.7 months, efficacy events occurred in 12 patients (5.6%). We observed three (1.4%) cardiac deaths, two (0.9%) MIs, six (2.8%) strokes, and one (0.5%) definite ST. After switching from DT to NOAC monotherapy after 6.3 ± 1.7 months, there was no rebound of ischemic events. Bleeding events occurred in 34 patients (15.7%) mainly under DT, while bleeding was less during NOAC monotherapy. In this long-term study of high-risk and real-world AF-patients with PCI, DT with NOAC and P2Y 12 inhibitor (6 months) followed by NOAC monotherapy was safe and effective.

Use and Outcomes of Antiarrhythmic Therapy in Patients with Atrial Fibrillation Receiving Oral Anticoagulation: Results from the ROCKET AF Trial

PubMed Central

Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Halperin, Jonathan L.; Breithardt, Günter; Passman, Rod; Hankey, Graeme J.; Patel, Manesh R.; Becker, Richard C.; Singer, Daniel E.; Hacke, Werner; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

2014-01-01

Background Antiarrhythmic drugs (AAD) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. Objective We aimed to study the use and outcomes of AAD therapy in anticoagulated AF patients. Methods Patients in the ROCKET AF trial (n=14,264) were grouped by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across groups, as well as across treatment assignment (rivaroxaban or warfarin). Results Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone, 537 [3.8%] with other AADs). Amiodarone-treated patients were less-often female (38% vs. 48%), had more persistent AF (64% vs. 40%), and more concomitant heart failure (71% vs. 41%) than patients receiving other AADs. Patients receiving no AAD more closely-resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone versus no AAD (50% vs. 58%, p<0.0001). Compared with no AAD, neither amiodarone (adjusted HR 0.98, 95% CI 0.74–1.31, p=0.9) nor other AADs (adjusted HR 0.66, 95% CI 0.37–1.17, p=0.15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Rivaroxaban treatment effects in patients not on an AAD were consistent with the overall trial (primary endpoint adjusted HR 0.82, 95% CI 0.68–0.98, pinteraction=0.06; safety endpoint adjusted HR 1.12, 95% CI 0.90–1.24, pinteraction=0.33). Conclusion Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The influence of amiodarone on outcomes in patients receiving rivaroxaban requires further study. PMID:24833235

Inverse-consistent rigid registration of CT and MR for MR-based planning and adaptive prostate radiation therapy

NASA Astrophysics Data System (ADS)

Rivest-Hénault, David; Dowson, Nicholas; Greer, Peter; Dowling, Jason

2014-03-01

MRI-alone treatment planning and adaptive MRI-based prostate radiation therapy are two promising techniques that could significantly increase the accuracy of the curative dose delivery processes while reducing the total radiation dose. State-of-the-art methods rely on the registration of a patient MRI with a MR-CT atlas for the estimation of pseudo-CT [5]. This atlas itself is generally created by registering many CT and MRI pairs. Most registration methods are not symmetric, but the order of the images influences the result [8]. The computed transformation is therefore biased, introducing unwanted variability. This work examines how much a symmetric algorithm improves the registration. Methods: A robust symmetric registration algorithm is proposed that simultaneously optimises a half space transform and its inverse. During the registration process, the two input volumetric images are transformed to a common position in space, therefore minimising any computational bias. An asymmetrical implementation of the same algorithm was used for comparison purposes. Results: Whole pelvis MRI and CT scans from 15 prostate patients were registered, as in the creation of MR-CT atlases. In each case, two registrations were performed, with different input image orders, and the transformation error quantified. Mean residuals of 0.63±0.26 mm (translation) and (8.7±7.3) × 10--3 rad (rotation) were found for the asymmetrical implementation with corresponding values of 0.038±0.039 mm and (1.6 ± 1.3) × 10--3 rad for the proposed symmetric algorithm, a substantial improvement. Conclusions: The increased registration precision will enhance the generation of pseudo-CT from MRI for atlas based MR planning methods.

Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review.

PubMed

Samuelson, Bethany T; Cuker, Adam; Siegal, Deborah M; Crowther, Mark; Garcia, David A

2017-01-01

Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban. PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results. We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r 2  = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r 2  = 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban. An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available. Copyright © 2016 American College of Chest Physicians. Published by Elsevier

Outpatient management of oral vitamin K antagonist therapy: defining and measuring high-quality management.

PubMed

Phillips, Katherine W; Ansell, Jack

2008-01-01

Oral anticoagulation therapy with warfarin is the mainstay of prevention and treatment of thromboembolic disease. However, it remains one of the leading causes of harmful medication errors and medication-related adverse events. The beneficial outcomes of oral anticoagulation therapy are directly dependent upon the quality of dose and anticoagulation management, but the literature is not robust with regards to what constitutes such management. This review focuses on, and attempts to define, the parameters of high-quality anticoagulation management and identifies the appropriate outcome measures constituting high-quality management. Elements discussed include the most fundamental measure, time in therapeutic range, along with other parameters including therapy initiation, time to therapeutic range, dosing management when patients are not in therapeutic range, perioperative dosing management, patient education, and other important outcome measures. Healthcare providers who manage oral anticoagulation therapy should utilize these parameters as a measure of their performance in an effort to achieve high-quality anticoagulation management.

Anticoagulation management associated with extracorporeal circulation.

PubMed

Sniecinski, Roman M; Levy, Jerrold H

2015-06-01

The use of extracorporeal circulation requires anticoagulation to maintain blood fluidity throughout the circuit, and to prevent thrombotic complications. Additionally, adequate suppression of hemostatic activation avoids the unnecessary consumption of coagulation factors caused by the contact of blood with foreign surfaces. Cardiopulmonary bypass represents the greatest challenge in this regard, necessitating profound levels of anticoagulation during its conduct, but also quick, efficient reversal of this state once the surgical procedure is completed. Although extracorporeal circulation has been around for more than half a century, many questions remain regarding how to best achieve anticoagulation for it. Although unfractionated heparin is the predominant agent used for cardiopulmonary bypass, the amount required and how best to monitor its effects are still unresolved. This review discusses the use of heparin, novel anticoagulants, and the monitoring of anticoagulation during the conduct of cardiopulmonary bypass. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thrombosis, Hypercoagulable States, and Anticoagulants.

PubMed

Hollenhorst, Marie A; Battinelli, Elisabeth M

2016-12-01

Patients with derangements of secondary hemostasis resulting from inherited or acquired thrombophilias are at increased risk of venous thromboemboli (VTE). Evaluation of a patient with suspected VTE proceeds via evidence-based algorithms that involve computing a pretest probability based on the history and physical examination; this guides subsequent work-up, which can include D dimer and/or imaging. Testing for hypercoagulable disorders should be pursued only in patients with VTE with an increased risk for an underlying thrombophilia. Direct oral anticoagulants are first-line VTE therapies, but they should be avoided in patients who are pregnant, have active cancer, antiphospholipid antibody syndrome, severe renal insufficiency, or prosthetic heart valves. Copyright © 2016 Elsevier Inc. All rights reserved.

An improved optical flow tracking technique for real-time MR-guided beam therapies in moving organs

NASA Astrophysics Data System (ADS)

Zachiu, C.; Papadakis, N.; Ries, M.; Moonen, C.; de Senneville, B. Denis

2015-12-01

Magnetic resonance (MR) guided high intensity focused ultrasound and external beam radiotherapy interventions, which we shall refer to as beam therapies/interventions, are promising techniques for the non-invasive ablation of tumours in abdominal organs. However, therapeutic energy delivery in these areas becomes challenging due to the continuous displacement of the organs with respiration. Previous studies have addressed this problem by coupling high-framerate MR-imaging with a tracking technique based on the algorithm proposed by Horn and Schunck (H and S), which was chosen due to its fast convergence rate and highly parallelisable numerical scheme. Such characteristics were shown to be indispensable for the real-time guidance of beam therapies. In its original form, however, the algorithm is sensitive to local grey-level intensity variations not attributed to motion such as those that occur, for example, in the proximity of pulsating arteries. In this study, an improved motion estimation strategy which reduces the impact of such effects is proposed. Displacements are estimated through the minimisation of a variation of the H and S functional for which the quadratic data fidelity term was replaced with a term based on the linear L1norm, resulting in what we have called an L2-L1 functional. The proposed method was tested in the livers and kidneys of two healthy volunteers under free-breathing conditions, on a data set comprising 3000 images equally divided between the volunteers. The results show that, compared to the existing approaches, our method demonstrates a greater robustness to local grey-level intensity variations introduced by arterial pulsations. Additionally, the computational time required by our implementation make it compatible with the work-flow of real-time MR-guided beam interventions. To the best of our knowledge this study was the first to analyse the behaviour of an L1-based optical flow functional in an applicative context: real-time MR

Risk factors for postpolypectomy bleeding in patients receiving anticoagulation or antiplatelet medications.

PubMed

Lin, David; Soetikno, Roy M; McQuaid, Kenneth; Pham, Chi; Doan, Gilbert; Mou, Shanshan; Shergill, Amandeep K; Somsouk, Ma; Rouse, Robert V; Kaltenbach, Tonya

2018-04-01

Balancing the risks for thromboembolism and postpolypectomy bleeding in patients requiring anticoagulation and antiplatelet agents is challenging. We investigated the incidence and risk factors for postpolypectomy bleeding on anticoagulation, including heparin bridge and other antithrombotic therapy. We performed a retrospective cohort and case control study at 2 tertiary-care medical centers from 2004 to 2012. Cases included male patients on antithrombotics with hematochezia after polypectomy. Nonbleeding controls were matched to cases 3 to 1 by antithrombotic type, study site, polypectomy technique, and year of procedure. Our outcomes were the incidence and risk factors for postpolypectomy bleeding. There were 59 cases and 174 matched controls. Postpolypectomy bleeding occurred in 14.9% on bridge anticoagulation. This was significantly higher than the overall incidence of bleeding on antithrombotics at 1.19% (95% confidence interval, 0.91%-1.54%) (59/4923). We identified similarly low rates of bleeding in patients taking warfarin (0.66%), clopidogrel (0.84%), and aspirin (0.92%). Patients who bled tended to have larger polyps (13.9 vs 7.3 mm; P < .001) and more polyps ≥2 cm (41% vs 10%; P < .001). Bleeding risk was increased with restarting antithrombotics within 1 week postpolypectomy (odds ratio [OR] 4.50; P < .001), having polyps ≥2 cm (OR 5.94; P < .001), performing right-sided cautery (OR 2.61; P = .004), and having multiple large polyps (OR 2.92; P = .001). Among patients on warfarin, the presence of bridge anticoagulation was an independent risk factor for postpolypectomy bleeding (OR 12.27; P = .0001). We conclude that bridge anticoagulation is associated with a high incidence of postpolypectomy bleeding and is an independent risk factor for hemorrhage compared with patients taking warfarin alone. A higher threshold to use bridge anticoagulation should be considered in patients with an elevated bleeding risk. Copyright © 2018. Published by

MR thermometry analysis program for laser- or high-intensity focused ultrasound (HIFU)-induced heating at a clinical MR scanner

NASA Astrophysics Data System (ADS)

Kim, Eun Ju; Jeong, Kiyoung; Oh, Seung Jae; Kim, Daehong; Park, Eun Hae; Lee, Young Han; Suh, Jin-Suck

2014-12-01

Magnetic resonance (MR) thermometry is a noninvasive method for monitoring local temperature change during thermal therapy. In this study, a MR temperature analysis program was established for a laser with gold nanorods (GNRs) and high-intensity focused ultrasound (HIFU)-induced heating MR thermometry. The MR temperature map was reconstructed using the water proton resonance frequency (PRF) method. The temperature-sensitive phase difference was acquired by using complex number subtraction instead of direct phase subtraction in order to avoid another phase unwrapping process. A temperature map-analyzing program was developed and implemented in IDL (Interactive Data Language) for effective temperature monitoring. This one program was applied to two different heating devices at a clinical MR scanner. All images were acquired with the fast spoiled gradient echo (fSPGR) pulse sequence on a 3.0 T GE Discovery MR750 scanner with an 8-channel knee array coil or with a home-built small surface coil. The analyzed temperature values were confirmed by using values simultaneously measured with an optical temperature probe (R2 = 0.996). The temperature change in small samples induced by a laser or by HIFU was analyzed by using a raw data, that consisted of complex numbers. This study shows that our MR thermometry analysis program can be used for thermal therapy study with a laser or HIFU at a clinical MR scanner. It can also be applied to temperature monitoring for any other thermal therapy based on the PRF method.

[Physicians' Opinion on Health Care in Oral Anticoagulation].

PubMed

Eggebrecht, Lisa; Prochaska, Jürgen H; Schleuter, Leonie; Nagler, Markus; Hardt, Roland; Schinzel, Helmut; Münzel, Thomas; Wild, Philipp S

2018-05-01

 The introduction of direct oral anticoagulants (DOAC) in addition to the established Vitamin K antagonist (VKA) has increased the complexity of antithrombotic therapy leading to numerous treatment options. Studies of the medical evaluation of the current treatment situation by health care providers, which are of great importance for the development of treatment strategies in addition to studies on pharmacovigilance, are limited in the literature.  11 700 physicians (Rhineland-Palatinate, Germany) were contacted to participate in the web-based survey on health care with oral anticoagulation (OAC). After detailed quality control, the study was analysed in synopsis with routine care data of VKA patients of the thrombEVAL study programme (N = 2.011).  In total, 512 physicians (mean age: 48.0 ± 9.6 years; 74.0 % male) participated in the study. In general, quality of OAC therapy was rated as "average/satisfactory" (2.9 ± 0.9). Comparison of physicians' perception with data from routine care highlighted marked differences regarding time in therapeutic range (+ 6.4 % [95 %-CI 2.7 %; 9.5 %]), duration of control intervals (- 35.0 % [28.0 %; 41.4 %]) and rate of OAC-related complications (+ 61.8 [37.8 %; 83.3 %], which differed additionally and statistically-significant between physician groups. The willingness to use DOAC was approximately 50 % lower in general physicians as compared to specialists (36.6 % [25.4 %; 47.8 %] vs. 72.4 % [66.0 %; 78.9 %]; p < 0.0001). Regarding management of OAC therapy, 73.8 % [69.7 %; 77.9 %] advocated the establishment of a service hotline and 67.3 % [62,9 %; 71.6 %] a specialized coagulation service.  The present survey among physicians reveals a need for optimization of OAC therapy in daily practice. Specialized care models might facilitate optimized OAC therapy with both VKAs and DOACs. © Georg Thieme Verlag KG Stuttgart · New York.

Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

PubMed

DiMarco, John P; Flaker, Gregory; Waldo, Albert L; Corley, Scott D; Greene, H Leon; Safford, Robert E; Rosenfeld, Lynda E; Mitrani, Gladys; Nemeth, Margit

2005-04-01

Stroke and systemic thromboembolism are serious problems for patients with atrial fibrillation (AF), but their incidence can be substantially reduced by appropriate anticoagulation. Bleeding is the major complication of anticoagulant treatment, and the relative risks for bleeding vs stroke must be considered when starting anticoagulation. The AFFIRM trial included patients with AF and at least one risk factor for stroke, randomly assigning them to either a rate-control or rhythm-control strategy. All patients were initially treated with warfarin. The incidence of protocol-defined major and minor bleeding was documented during follow-up. Variables associated with bleeding were determined using a Cox proportional hazards model, using baseline and time-dependent covariates. The 4060 patients in the AFFIRM trial were followed for an average of 3.5 years. Major bleeding occurred in 260 patients, an annual incidence of approximately 2% per year, with no significant difference between the rate-control and rhythm-control groups. Increased age, heart failure, hepatic or renal disease, diabetes, first AF episode, warfarin use, and aspirin use were significantly associated with major bleeding. Minor bleeding was common in both treatment arms, with 738 patients reporting this problem in one or more visits. Bleeding is a significant problem that complicates management of patients with AF. Risk factors for bleeding can be identified, and knowledge of these risk factors can be used to plan therapy.

Anticoagulation and high dose liver radiation. A preliminary report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lightdale, C.J.; Wasser, J.; Coleman, M.

Two groups of patients were observed for evidence of acute radiation hepatitis during high dose radiation to the liver. The first group of 18 patients with metastatic liver disease received an average of 4,050 rad to the whole liver. Half received anticoagulation with warfarin. One patient on anticoagulation developed evidence of acute radiation hepatitis while 2 patients did so without anticoagulation. Eleven patients with Hodgkin's disease received 4,000 rad to the left lobe of the liver during extended field radiation. Four of these 11 patients were anticoagulated to therapeutic range. Only one of the fully anticoagulated patients showed changes onmore » liver scan consistent with radiation hepatitis whereas three did so without anticoagulation. No serious sequelae from anticoagulation occurred in either group. These preliminary data suggest that anticoagulation may be safely administered with high dose hepatic radiation and that further trials with anticoagulation are warranted.« less

Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis.

PubMed

van Walraven, Carl; Hart, Robert G; Singer, Daniel E; Laupacis, Andreas; Connolly, Stuart; Petersen, Palle; Koudstaal, Peter J; Chang, Yuchiao; Hellemons, Beppie

2002-11-20

differ but appeared to improve for oral anticoagulant patients 3 years after therapy was started. Compared with aspirin, oral anticoagulant significantly decreases the risk of all strokes, ischemic strokes, and cardiovascular events for patients with nonvalvular chronic or paroxysmal AF but modestly increases the absolute risk of major bleeding. The balance of benefits and risks varies by patient subgroup.

Whole-body hybrid imaging concept for the integration of PET/MR into radiation therapy treatment planning.

PubMed

Paulus, Daniel H; Oehmigen, Mark; Grüneisen, Johannes; Umutlu, Lale; Quick, Harald H

2016-05-07

Modern radiation therapy (RT) treatment planning is based on multimodality imaging. With the recent availability of whole-body PET/MR hybrid imaging new opportunities arise to improve target volume delineation in RT treatment planning. This, however, requires dedicated RT equipment for reproducible patient positioning on the PET/MR system, which has to be compatible with MR and PET imaging. A prototype flat RT table overlay, radiofrequency (RF) coil holders for head imaging, and RF body bridges for body imaging were developed and tested towards PET/MR system integration. Attenuation correction (AC) of all individual RT components was performed by generating 3D CT-based template models. A custom-built program for μ-map generation assembles all AC templates depending on the presence and position of each RT component. All RT devices were evaluated in phantom experiments with regards to MR and PET imaging compatibility, attenuation correction, PET quantification, and position accuracy. The entire RT setup was then evaluated in a first PET/MR patient study on five patients at different body regions. All tested devices are PET/MR compatible and do not produce visible artifacts or disturb image quality. The RT components showed a repositioning accuracy of better than 2 mm. Photon attenuation of  -11.8% in the top part of the phantom was observable, which was reduced to  -1.7% with AC using the μ-map generator. Active lesions of 3 subjects were evaluated in terms of SUVmean and an underestimation of  -10.0% and  -2.4% was calculated without and with AC of the RF body bridges, respectively. The new dedicated RT equipment for hybrid PET/MR imaging enables acquisitions in all body regions. It is compatible with PET/MR imaging and all hardware components can be corrected in hardware AC by using the suggested μ-map generator. These developments provide the technical and methodological basis for integration of PET/MR hybrid imaging into RT planning.

Progressively Worsening Premature Coronary Artery Disease: Adding Anticoagulation Stabilizes-Reverses Clinical Symptomatic Disease Progression in Thrombophilic-Atherothrombotic Patients: A Pilot Study.

PubMed

Rothschild, Matan; Jetty, Vybhav; Mahida, Christopher; Wang, Ping; Prince, Marloe; Goldenberg, Naila; Glueck, Charles J

2017-11-01

In 35 patients with 116 severe premature cardiovascular disease (CVD) events (median age: 48 years), 14 having worsening CVD despite maximal intervention, we evaluated thrombophilia and speculated that anticoagulation might arrest-reverse progressive thrombophilic-atherothrombotic CVD. Thrombophilia-hypofibrinolysis in the 35 patients was compared to 110 patients with venous thromboembolism (VTE) without CVD and to 110 healthy normal controls. Efficacy-safety of anticoagulation was prospectively assessed in 14 of the 35 patients whose CVD worsened over 2 years despite maximal medical-surgical intervention. At entry on maximally tolerated lipid-lowering therapy, median low-density lipoprotein was 88 mg/dL. Measures of thrombophilia-hypofibrinolysis in the 35 cases differed from 110 VTE controls only for the lupus anticoagulant, present in 6 (21%) of 28 cases versus 4 (4%) of 91 VTE controls ( P = .01), and for high anticardiolipin antibodies (ACLAs) immunoglobulin G, 5 (14%) of 35 cases versus 4 of 108 VTE controls (4%), P = .04. The 14 patients who were anticoagulated differed from 110 VTE controls only for the lupus anticoagulant, 38% versus 4%, P = .001, and for high lipoprotein (a), 46% versus 17%, P = .028, respectively. The 14 patients with atherothrombosis having inexorably worsening CAD despite maximal medical-surgical therapy were anticoagulated for 6.5 years (median), with clinical CVD progression arrested in 12 (86%), and all 12 became asymptomatic. In the 35 patients with premature CVD, thrombophilia was pervasive, comparable to or more severe than in VTE controls without CVD. When CVD progressively worsens despite maximal intervention, thrombophilia and atherosclerosis (atherothrombosis) are commonly concurrent, and the downhill course of CVD may be arrested-stabilized by anticoagulation.

Value of MR contrast media in image-guided body interventions.

PubMed

Saeed, Maythem; Wilson, Mark

2012-01-28

In the past few years, there have been multiple advances in magnetic resonance (MR) instrumentation, in vivo devices, real-time imaging sequences and interventional procedures with new therapies. More recently, interventionists have started to use minimally invasive image-guided procedures and local therapies, which reduce the pain from conventional surgery and increase drug effectiveness, respectively. Local therapy also reduces the systemic dose and eliminates the toxic side effects of some drugs to other organs. The success of MR-guided procedures depends on visualization of the targets in 3D and precise deployment of ablation catheters, local therapies and devices. MR contrast media provide a wealth of tissue contrast and allows 3D and 4D image acquisitions. After the development of fast imaging sequences, the clinical applications of MR contrast media have been substantially expanded to include pre- during- and post-interventions. Prior to intervention, MR contrast media have the potential to localize and delineate pathologic tissues of vital organs, such as the brain, heart, breast, kidney, prostate, liver and uterus. They also offer other options such as labeling therapeutic agents or cells. During intervention, these agents have the capability to map blood vessels and enhance the contrast between the endovascular guidewire/catheters/devices, blood and tissues as well as direct therapies to the target. Furthermore, labeling therapeutic agents or cells aids in visualizing their delivery sites and tracking their tissue distribution. After intervention, MR contrast media have been used for assessing the efficacy of ablation and therapies. It should be noted that most image-guided procedures are under preclinical research and development. It can be concluded that MR contrast media have great value in preclinical and some clinical interventional procedures. Future applications of MR contrast media in image-guided procedures depend on their safety, tolerability

Venous Thromboembolism Requiring Extended Anticoagulation Among HIV-Infected Patients in a Rural, Resource-Constrained Setting in Western Kenya.

PubMed

Kanyi, John; Karwa, Rakhi; Pastakia, Sonak Dinesh; Manji, Imran; Manyara, Simon; Saina, Collins

2017-05-01

HIV-infected patients are at an increased risk of developing venous thromboembolism (VTE), and minimal data are available to describe the need for extended treatment. To evaluate the frequency of and determine predictive risk factors for extended anticoagulation of VTE in HIV-infected patients in rural, western Kenya. A retrospective chart review was conducted at the Anticoagulation Monitoring Service affiliated with Moi Teaching and Referral Hospital and the Academic Model Providing Access to Healthcare. Data were collected on patients who were HIV-infected and receiving anticoagulation for lower-limb deep vein thrombosis. The need for extended anticoagulation, defined as receiving ≥7 months of warfarin therapy, was established based on patient symptoms or Doppler ultrasound-confirmed diagnosis. Evaluation of the secondary outcomes utilized a univariate analysis to identify risk factors associated with extended anticoagulation. A total of 71 patients were included in the analysis; 27 patients (38%) required extended anticoagulation. The univariate analysis showed a statistically significant association between the need for extended anticoagulation and achieving a therapeutic international normalized ratio within 21 days in both the unadjusted and adjusted analysis. Patients with a history of opportunistic infections required an extended duration of anticoagulation in the adjusted analysis: odds ratio = 3.42; 95% CI = 1.04-11.32; P = 0.04. This study shows that there may be a need for increased duration of anticoagulation in HIV-infected patients, with a need to address the issue of long-term management. Guideline recommendations are needed to address the complexity of treatment issues in this population.

Relation of psychological distress to the international normalized ratio in patients with venous thromboembolism with and without oral anticoagulant therapy.

PubMed

Von Känel, R; Vökt, F; Biasiutti, F Demarmels; Stauber, S; Wuillemin, W A; Lukas, P S

2012-08-01

Psychological distress might affect the international normalized ratio (INR), but effects might vary depending on oral anticoagulant (OAC) therapy. To investigate the association of psychological distress with INR and clotting factors of the extrinsic pathway in patients with and without OAC therapy. We studied 190 patients with a previous venous thromboembolism (VTE); 148 had discontinued OAC therapy and 42 had ongoing OAC therapy. To assess psychological distress, all patients completed validated questionnaires to measure symptoms of depression, anxiety, worrying, anger and hostility. INR, fibrinogen, factor (F)II:C, FV:C, FVII:C and FX:C were measured as part of outpatient thrombophilia work-up. In VTE patients without OAC therapy, the odds of a reduced INR (< 1.00) were significantly increased from 1.5 to 1.8 times for an increase of 1 standard deviation (SD) in symptoms of depression, anxiety, worrying and anger, respectively, after adjusting for gender, age, body mass index, socioeconomic status, hematocrit and C-reactive protein. Worrying, anger and hostility also showed significant direct associations with FVII:C. In patients with OAC therapy, INR was unrelated to a negative affect; however, lower FVII:C related to anxiety and worrying as well as lower FX:C related to anger and hostility were observed in patients with OAC therapy compared with those without OAC therapy. Psychological distress was associated with a reduced INR in VTE patients without OAC therapy. The direction of the association between psychological distress and activity in some clotting factors of the extrinsic coagulation pathway might differ depending on whether VTE patients are under OAC therapy or not. © 2012 International Society on Thrombosis and Haemostasis.

Cost-effectiveness of pharmacogenetics-guided warfarin therapy vs. alternative anticoagulation in atrial fibrillation.

PubMed

Pink, J; Pirmohamed, M; Lane, S; Hughes, D A

2014-02-01

Pharmacogenetics-guided warfarin dosing is an alternative to standard clinical algorithms and new oral anticoagulants for patients with nonvalvular atrial fibrillation. However, clinical evidence for pharmacogenetics-guided warfarin dosing is limited to intermediary outcomes, and consequently, there is a lack of information on the cost-effectiveness of anticoagulation treatment options. A clinical trial simulation of S-warfarin was used to predict times within therapeutic range for different dosing algorithms. Relative risks of clinical events, obtained from a meta-analysis of trials linking times within therapeutic range with outcomes, served as inputs to an economic analysis. Neither dabigatran nor rivaroxaban were cost-effective options. Along the cost-effectiveness frontier, in relation to clinically dosed warfarin, pharmacogenetics-guided warfarin and apixaban had incremental cost-effectiveness ratios of £13,226 and £20,671 per quality-adjusted life year gained, respectively. On the basis of our simulations, apixaban appears to be the most cost-effective treatment.

Use of Oral Anticoagulant Therapy in Older Adults with Atrial Fibrillation after Acute Ischemic Stroke

PubMed Central

McGrath, Emer R.; Go, Alan S.; Chang, Yuchiao; Borowsky, Leila H.; Fang, Margaret C.; Reynolds, Kristi; Singer, Daniel E.

2016-01-01

Objective To explore barriers to anticoagulation among older atrial fibrillation (AF) patients at high risk for stroke and identify opportunities where interventions might increase use of oral anticoagulants (OAC). Design Retrospective cohort study Setting Two large community-based AF cohorts Participants 1405 patients (mean age 79 years) with ischemic stroke surviving hospitalization. Measurements Using structured chart review, we identified reasons for non-use of OACand assessed one-year post-stroke survival. Logistic regression identified correlates of OAC non-use. Results The median CHA2DS2-VASc score was 5, yet 44% of patients were not prescribed OAC at discharge. The most frequent (non-mutually exclusive) physician reasons for non-prescription of OAC included fall risk (26.7%), poor prognosis (19.3%), bleeding history (17.1%), patient/family refusal (14.9%), older age (11.0%) and dementia (9.4%). Older age (OR 8.96, 95% CI 5.01–16.04 for age ≥85 vs. age <65 years) and increased disability (OR 12.58, 95% CI 5.82–27.21 for severe vs. no deficit) were the most important independent predictors of non-use of OAC. By one year, 42.5% of those not receiving OAC at discharge had died versus 19.1% of those receiving OAC (p<0.0001), far higher than recurrent stroke rates. Conclusion Despite very high stroke risk, over 40% of patients were not discharged on OAC. Dominant reasons included fall risk, poor prognosis, older age, and dementia. These patients’ elevated 1-year mortality rate confirmed their high level of comorbidity. Future work to improve outcomes and clinical decisions regarding anticoagulation in this patient population should focus on: mitigation of fall risk, better assessment and decision tools for determining risk/benefit in individual patients, and determining whether newer anticoagulants are safer in complex elderly and/or frail patients. PMID:28039855

[Anticoagulation in polypathological patients with atrial fibrillation].

PubMed

Díez-Manglano, Jesús; Bernabeu-Wittel, Máximo; Barón-Franco, Bosco; Murcia-Zaragoza, José; Fuertes Martín, Aurelio; Alemán, Antonio; Ollero-Baturone, Manuel

2013-02-02

To determine the use of oral anticoagulants in polypathological patients with atrial fibrillation and its influence on mortality and loss of functionality. Patients with polypathological patient criteria and atrial fibrillation were included in an observational, prospective and multicenter study. Data on demographic, clinical, functional and sociofamilial characteristics, CHADS2 score, levels of hemoglobin, albumin and creatinine, use of oral anticoagulants and survival and functional status at one year were collected. Five hundred and thirty-two (32.6%) of 1,632 polypathological patients had atrial fibrillation. The stroke risk was high in 505 (94.9%), moderate in 24 (4.5%) and low in 3 (0.6%) patients. Oral anticoagulants were used in 61% of patients with CHADS2 score≥2 and in 37.5% with CHADS2 score=1. Oral anticoagulants were less used in older patients, with more functional and cognitive impairment. Heart failure was associated with more use of oral anticoagulants. There was no difference by the presence of hypertension, diabetes, anemia, renal insufficiency or stroke. In multivariate analysis the use of oral anticoagulants was independently associated with lower age, lower cognitive impairment, absence of hepatic disease and with higher stroke risk. The prescription of oral anticoagulants was independently associated with more survival at one year with no influence on functional status. Oral anticoagulants are underused in polypathological patients with atrial fibrillation despite being associated with more survival. Copyright © 2012 Elsevier España, S.L. All rights reserved.

The role of oral anticoagulants in epistaxis.

PubMed

Buchberger, A M S; Baumann, A; Johnson, F; Peters, N; Piontek, G; Storck, K; Pickhard, A

2018-06-23

The purpose of this retrospective study was to identify the impact of oral anticoagulants on epistaxis with the focus on new oral anticoagulants. The study was conducted at the Department  for Ear- Nose- and Throat (ENT), Head and Neck Surgery, Technical University Munich, Germany. All patients presenting in 2014 with the diagnosis of epistaxis to a specialized ENT accident and emergency department were identified and analyzed in clinical data and medication. 600 adult cases, with a median age of 66.6 years were identified with active bleeding. 66.8% of all cases were anticoagulated. Classic oral anticoagulants (COAC) were three times more common in patients than new-generation oral anticoagulants (NOAC). Recurrent bleeding was significantly associated with oral anticoagulants (OAC) (p = 0.014) and bleeding location was most often anterior (p = 0.006). In contrast, severe cases, which required surgery or embolization were significantly more likely in non-anticoagulated middle-aged patients with posterior bleedings (p < 0.05). In our epistaxis cohort, OAC were highly overrepresented (40%) when compared to the general German population (1%) but COAC as well as NOAC played only a minor role in severe courses of epistaxis. Oral anticoagulation, especially with new-generation drugs, is not associated with more complicated and severe courses of epistaxis, but rather with recurrent bleeding. One should keep this information in mind when triaging the patient in the emergency room and when planning further procedures.

2017 Scientific Sessions Sol Sherry Distinguished Lecture in Thrombosis: Factor XI as a Target for New Anticoagulants.

PubMed

Weitz, Jeffrey I; Fredenburgh, James C

2018-02-01

The goal of anticoagulant therapy is to attenuate thrombosis without compromising hemostasis. Although the direct oral anticoagulants are associated with less intracranial hemorrhage than vitamin K antagonists, bleeding remains their major side effect. Factor XI has emerged as a promising target for anticoagulants that may be safer than those currently available. The focus on factor XI stems from epidemiological evidence of its role in thrombosis, the observation of attenuated thrombosis in factor XI-deficient mice, identification of novel activators, and the fact that factor XI deficiency is associated with only a mild bleeding diathesis. Proof-of-concept comes from the demonstration that compared with enoxaparin, factor XI knockdown reduces venous thromboembolism without increasing bleeding after elective knee arthroplasty. This article rationalizes the selection of factor XI as a target for new anticoagulants, reviews the agents under development, and outlines a potential path forward for their development. © 2017 American Heart Association, Inc.

The role of heparin in sepsis: much more than just an anticoagulant.

PubMed

Li, Xu; Ma, Xiaochun

2017-11-01

Despite progress in antibiotic treatment, mechanical ventilation, fluid resuscitation and blood glucose maintenance, sepsis remains a cause of high mortality in the intensive care unit to date, there are no proven treatment strategies for the routine management of septic patients. The extensive interaction between inflammation and coagulation contributes to the basic pathophysiology of sepsis. Thus, the agents that attenuate the activation of both inflammation and coagulation may improve the outcome in sepsis. Apart from the well-known anticoagulant effects of heparin, it also possesses various immunomodulatory properties and protects glycocalyx from shedding. Hence, heparin seems to be such an agent. Immunothrombosis plays an important role in early host defence against bacterial dissemination, thus the proper timing for anticoagulant therapy should be determined. We review the available experimental and clinical data supporting the use of heparin in sepsis. At this time the use of heparin in the treatment of sepsis is conflicting. Future trials of heparin therapy for sepsis should concentrate on the very severely ill patients, in whom benefit is most likely to be demonstrated. © 2017 John Wiley & Sons Ltd.

Anticoagulants in ischemia-guided management of non-ST-elevation acute coronary syndromes.

PubMed

Mayer, Martin

2017-03-01

The most recent joint guidelines from the American Heart Association (AHA) and American College of Cardiology (ACC) on the management of non-ST-elevation acute coronary syndromes (NSTE-ACS) are a result of a substantial and considered undertaking, and those involved deserve much recognition for their efforts. However, the handling of anticoagulants seems somewhat inadequate, and this is a highly-relevant matter when managing NSTE-ACS. Among areas of potential uncertainty, emergency medicine professionals might still be left wondering about the particulars of anticoagulant therapy when pursuing ischemia-guided management of NSTE-ACS (that is, managing NSTE-ACS without an intent for early invasive measures, such as coronary angiography and revascularization). This review seeks to provide insight into this question. Relevant clinical trials are appraised and translated into clinical context for emergency medicine professionals, including the implications of noteworthy advancements in the management of NSTE-ACS. Although current guidelines from the AHA and ACC suggest enoxaparin has better evidence than other anticoagulants in the setting of NSTE-ACS management, careful review of the evidence shows this is not actually clearly supported by the available evidence in the era of contemporary management. Unless and until better contemporary data emerge, emergency medicine professionals must carefully weigh the available evidence, its limitations, and the possible clinical implications of the various anticoagulant options when managing NSTE-ACS. Copyright © 2017 Elsevier Inc. All rights reserved.

Attitudes and Preferences on the Use of Mobile Health Technology and Health Games for Self-Management: Interviews With Older Adults on Anticoagulation Therapy

PubMed Central

Nguyen, Annie Lu; Berg, Jill; Amin, Alpesh; Bachman, Mark; Guo, Yuqing; Evangelista, Lorraine

2014-01-01

Background Older adults are at substantial risk for cardiovascular disorders that may require anticoagulation therapy. Those on warfarin therapy report dissatisfaction and reduced quality of life (QOL) resulting from the treatment. Advances in the area of mobile health (mHealth) technology have resulted in the design and development of new patient-centric models for the provision of personalized health care services to improve care delivery. However, there is a paucity of research examining the effectiveness of mHealth tools on knowledge, attitudes, and patient satisfaction with treatment, as well as self-management, adherence to therapy, and QOL in older adults with chronic illness conditions requiring long-term warfarin therapy. Objective The objective of the study was to explore the attitudes and preferences of older adults on warfarin therapy regarding the use of mHealth technology and health games to gain skills for self-management. Methods We conducted group and individual interviews with patients (60 years or older) on warfarin therapy at two anticoagulation clinics affiliated with an academic medical center. We held 4 group and 2 individual interviews, resulting in 11 patient participants and 2 family caregiver participants. We used structured questions on three topic areas including medication self-management strategies, mHealth technology use, and health games for exercise. We demonstrated some commercial health apps related to medication management, vitamin K content of food, and a videogame for balance exercise. Discussions were audiotaped and transcribed verbatim. Common themes were drawn using content analysis. Results The participants reported awareness of the importance of staying on schedule with warfarin therapy. They also acknowledged that negative experiences of friends or family members who were taking warfarin influenced their desire to keep on schedule with warfarin therapy. In addition, the participants expressed that the use of m

TH-CD-BRA-08: Novel Iron-Based Radiation Reporting Systems as 4D Dosimeters for MR-Guided Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, H; Alqathami, M; Wang, J

Purpose: To compare novel radiation reporting systems utilizing ferric ion (Fe{sup 3+}) reduction versus ferrous ion (Fe{sup 2+}) oxidation in gelatin matrixes for 3D and 4D (3D+time) MR-guided radiation therapy dosimetry. Methods: Dosimeters were irradiated using an integrated 1.5T MRI and 7MV linear accelerator (MR-Linac). Dosimeters were read-out with both a spectrophotometer and the MRI component of the MR-Linac immediately after irradiation. Changes in optical density (OD) were measured using a spectrophotometer; changes in MR signal intensity due to the paramagnetic differences in the iron ions were measured using the MR-Linac in real-time during irradiation (balanced-FFE sequences) and immediately aftermore » irradiation (T{sub 1}-weighted and inversion recovery sequences). Results: Irradiation of Fe{sup 3+} reduction dosimeters resulted in a stable red color with an absorbance peak at 512 nm. The change in OD relative to dose exhibited a linear response up to 100 Gy (R{sup 2}=1.00). T{sub 1}-weighted-MR signal intensity (SI) changed minimally after irradiation with increases of 8.0% for 17 Gy and 9.7% after escalation to 35 Gy compared to the un-irradiated region. Irradiation of Fe{sup 2+} oxidation dosimeters resulted in a stable purple color with absorbance peaks at 440 and 585 nm. The changes in OD, T{sub 1}-weighted-MR SI, and R{sub 1} relative to dose exhibited a linear response up to at least 8 Gy (R{sup 2}=1.00, 0.98, and 0.99) with OD saturation above 40 Gy. The T{sub 1}-weighted-MR SI increased 50.3% for 17 Gy compared to the un-irradiated region. The change in SI was observed in both 2D+time and 4D (3D+time) acquisitions post-irradiation and in real-time during irradiation with a linear increase with respect to dose (R{sup 2}>0.93). Conclusion: The Fe{sup 2+} oxidation-based system was superior as 4D dosimeters for MR-guided radiation therapy due to its higher sensitivity in both optical and MR signal readout and feasibility for real-time 4D

Vena cava filter retrieval in therapeutically anticoagulated patients.

PubMed

Schmelzer, Thomas M; Christmas, A Britton; Taylor, Dennis A; Heniford, B Todd; Sing, Ronald F

2008-12-01

Vena cava filters (VCFs) are indicated in patients with active venous thromboembolism and are a contraindication to therapeutic anticoagulation. When patients can be anticoagulated, VCFs can be removed; however, patients often have anticoagulation discontinued during the retrieval procedure, leaving them at risk for pulmonary embolism (PE). The authors evaluated their experience with retrieving VCFs in therapeutically anticoagulated patients. Data from a prospectively collected database of patients with VCFs placed between January 2005 and September 2007 were reviewed. The retrievals in therapeutically anticoagulated patients (international normalized ratio, 2.0-3.4) were performed using a strict protocol, including preretrieval and postretrieval cavograms. All retrievals were performed in the operating room, and patients were discharged home the same day and examined within 7 to 14 days. Descriptive statistics including means and counts were calculated. One hundred thirteen VCF removals occurred during the study period; 62 were attempted on anticoagulated patients (42 male and 20 female patients; mean age, 36.5 years). Thirty-five patients (56%) had VCFs placed for prophylaxis, 22 (35%) had deep venous thromboses or PEs but had contraindications to anticoagulation, and 5 (8%) were on anticoagulation, which was discontinued perioperatively for major surgical operations. The mean time the filters were in place was 153.7 days (range, 22-684 days). No extravasation was seen on postretrieval cavography. Eight of 62 removal attempts in anticoagulated patients were unsuccessful. One patient had a postoperative pneumothorax that was successfully managed without intervention. There were no operative bleeding complications, and no hematomas or contusions were seen at follow-up. The retrieval of VCFs in therapeutically anticoagulated patients can be performed without complication. Given the perioperative risk for PE, anticoagulation should not be discontinued for VCF

Inadvertent exaggerated anticoagulation following use of bismuth subsalicylate in an enterally fed patient receiving warfarin therapy.

PubMed

Bingham, Angela L; Brown, Rex O; Dickerson, Roland N

2013-12-01

We report a case of an inadvertent increase in the international normalized ratio (INR) after the addition of bismuth subsalicylate for the treatment of diarrhea in an enterally fed patient receiving warfarin therapy. A 56-year-old Caucasian female presented to the trauma intensive care unit (ICU) with multiple lower extremity fractures. Warfarin was initiated for deep vein thrombosis prophylaxis due to the patient's inability to ambulate. The target INR was 2-3. Continuous intragastric enteral feeding was withheld 1 hour before and 1 hour after intragastric administration of warfarin. Bismuth subsalicylate 30 mL every 4 hours was prescribed for diarrhea. Within 3 days after starting bismuth subsalicylate therapy, the patient's INR increased from 2.56 to 3.54 and minor bleeding was noted from the patient's tracheostomy site. No significant change in warfarin dosage, variability in vitamin K intake, or medications that potentially alter warfarin metabolism were present during the unexpected rise in INR. When the bismuth subsalicylate was discontinued, the patient's INR stabilized into the target range on the same warfarin dose given at the time of the supratherapeutic INR. Salicylate displaces warfarin from plasma protein binding sites and may result in a significant increase in INR secondary to redistribution of warfarin to the free active form. Evaluation of this case report using the Drug Interaction Probability Scale and Naranjo Adverse Drug Reaction Probability Scale yielded scores consistent with a probable adverse drug interaction. Bismuth subsalicylate exaggerates warfarin's anticoagulant response and its concurrent use during warfarin therapy should be avoided.

Reduced Anticoagulant Effect of Dabigatran in a Patient Receiving Concomitant Phenytoin.

PubMed

Wiggins, Barbara S; Northup, Amanda; Johnson, Dominic; Senfield, Jeffrey

2016-02-01

Dabigatran, a direct thrombin inhibitor, is an oral anticoagulant indicated for the prevention of stroke in patients with atrial fibrillation (AF) and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. Dabigatran, as well as the other new anticoagulants-rivaroxaban, apixaban, and edoxaban-are substrates for P-glycoprotein (P-gp). Although the U.S. labeling for rivaroxaban and apixaban states to avoid concomitant use with phenytoin, a known P-gp inducer, the U.S. labeling for dabigatran and edoxaban are less clear. We describe the first case report, to our knowledge, documenting a drug interaction between phenytoin and dabigatran by using laboratory measurements of dabigatran serum concentrations. A 45-year-old African-American man was admitted to the inpatient cardiology service following defibrillations from his implantable cardioverter defibrillator. The patient was evaluated and received appropriate antitachycardia pacing for atrial tachyarrhythmias for an episode of ventricular tachycardia (VT), and antiarrhythmic therapy with sotalol was initiated to reduce both his AF and VT burden. On review of the patient's medications for potential interactions, it was discovered that the patient was taking both dabigatran and phenytoin. To determine the magnitude of this drug interaction prior to making a change in his anticoagulation regimen, a dabigatran serum concentration was measured. This concentration was undetectable, indicating that phenytoin had a significant influence on dabigatran's metabolism and that this patient was at high risk for stroke. Clinicians should be aware of this interaction between phenytoin and dabigatran as well as with all other new oral anticoagulants. In patients taking phenytoin who require an anticoagulant, only warfarin should be prescribed to minimize the risk of stroke. In addition, the prescribing information for dabigatran should be updated to include other medications that result in a significant

A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free liver dialysis by the Molecular Adsorbents Recirculating System

PubMed Central

2012-01-01

Introduction The Molecular Adsorbent Recycling System (MARS) is used to treat patients with liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens. Methods We performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55 ± 11 years) with liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher's exact test was used for contingency table analysis. Results Of a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher's exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P < 0.001) but remained within a safe range. We observed no major adverse events. Conclusions Regional citrate anticoagulation in patients with liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with

Secondary poisoning of owls by anticoagulant rodenticides

USGS Publications Warehouse

Mendenhall, Vivian M.; Pank, L.F.

1980-01-01

Anticoagulants-compounds that prevent clotting of the blood-are extensively used for control of small mammal pests. The potential secondary hazards of 6 anticoagulant rodenticides to birds of prey were examined in this study. Whole rats or mice were killed with each anticoagulant and were fed to 1-3 species of owls. Owls died of hemorrhaging after feeding on rats killed with bromadiolone, brodifacoum, or diphacinone; sublethal hemorrhaging occurred in owls fed rats killed with difenacoum. These results demonstrate potential secondary hazards of 4 anticoagulants to avian predators. No abnormalities were observed in owls fed rats killed with fumarin and chlorophacinone

Technology-assisted self-testing and management of oral anticoagulation therapy: a qualitative patient-focused study.

PubMed

Kuljis, Jasna; Money, Arthur G; Perry, Mark; Barnett, Julie; Young, Terry

2017-09-01

Oral anticoagulation therapy requires regular blood testing to ensure therapeutic levels are maintained and excessive bleeding/clotting is avoided. Technology-assisted self-testing and management is seen as one of the key areas in which quality of care can be improved whilst reducing costs. Nevertheless, levels of patient engagement in self-testing and management remain low. To date, little research emphasis has been placed on understanding the patients' perspectives for low engagement. The typical approach adopted by healthcare providers is to provide patient education programmes, with the expectation that individual patients will change their behaviour and adopt new self-care strategies. However, if levels of patient engagement are to be increased, healthcare providers must also develop a better understanding of how their clinical service provision is perceived by patients and make adaptations. To explore patient views, needs and expectations of an anticoagulation service and the self-testing and management services provided. Interviews were conducted with 17 patients who currently engage in international normalised ratio (INR) self-testing and management. Thematic coding and analysis were carried out on the interview transcripts. Four high-level themes emerged from interviews: (i) role of clinic, (ii) motivations for self-testing, (iii) managing INR and (iv) trust. The clinic was seen as adding value in terms of specifying testing frequency, dosage profiles and calibrating equipment. Prompt communication from clinic to patient was also valued, although more personalised/real-time communication would help avoid feelings of isolation. Patients felt more in control as self-tester/managers and often took decisions about treatment adjustments themselves. However, some also manipulated their own test results to avoid 'unnecessary' interventions. More personalised/real-time communication, pragmatic and collaborative patient-clinician partnerships and recognition of

Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True?: A Systematic Review.

PubMed

Violi, Francesco; Lip, Gregory Yh; Pignatelli, Pasquale; Pastori, Daniele

2016-03-01

Educational advice is often given to patients starting treatment with vitamin K Antagonists (VKAs). A great emphasis is made on nutritional information. Common belief is that dietary vitamin K intake could counteract the anticoagulant effect by VKAs and for many years, patients have been discouraged to consume vitamin-K-rich foods, such as green leafy vegetables.The objective of this study is to summarize the current evidence supporting the putative interaction between dietary vitamin K intake and changes in INR with the VKAs.Data sources are MEDLINE via PubMed and Cochrane database.All clinical studies investigating the relationship between dietary vitamin K and measures of anticoagulation were included. We excluded all studies of supplementation of vitamin K alone.We performed a systematic review of the literature up to October 2015, searching for a combination of "food," "diet," "vitamin K," "phylloquinone," "warfarin," "INR," "coagulation," and "anticoagulant."Two dietary interventional trials and 9 observational studies were included. We found conflicting evidence on the effect of dietary intake of vitamin K on coagulation response. Some studies found a negative correlation between vitamin K intake and INR changes, while others suggested that a minimum amount of vitamin K is required to maintain an adequate anticoagulation. Median dietary intake of vitamin K1 ranged from 76 to 217 μg/day among studies, and an effect on coagulation may be detected only for high amount of vitamin intake (>150 μg/day).Most studies included patients with various indications for VKAs therapy, such as atrial fibrillation, prosthetic heart valves, and venous thromboembolism. Thus, INR target was dishomogeneous and no subanalyses for specific populations or different anticoagulants were conducted. Measures used to evaluate anticoagulation stability were variable.The available evidence does not support current advice to modify dietary habits when starting therapy with VKAs

[MR Imaging of the pelvis in the diagnosis of the endometrium in breast cancer patients in tamoxifen therapy].

PubMed

Hauth, E; Libera, H; Kimmig, R; Forsting, M

2006-03-01

The purpose of the study was to determine the value of MR imaging of the pelvis in the diagnostic work-up of the endometrium in breast cancer patients in tamoxifen therapy. MR imaging of the pelvis was performed on 24 patients (mean: 62 years, range: 51 - 74 years) and 30 healthy women (mean: 65 years, range: 51 - 73 years). The volume of the uterus and cervix and the maximal thickness of the endometrium, junctional zone and myometrium of the uterus were determined and compared to the confidence interval of the parameters in healthy women. The Mann-Whitney U-test was used to identify differences in the volume of the uterus and cervix and in the thickness of the uterine wall layers in both groups. A comparison of the volume of the uterus and cervix and the thickness of the uterine wall layers in the two groups yielded no significant differences. The volume of the uterus and cervix showed no statistical differences between the two groups. The maximal height of the endometrium in the patient group showed a mean of 0.6 cm (range: 0.1 - 2.2 cm), and a mean of 0.4 cm (range: 0.1 - 1.2 cm) in the group of healthy women. The differences were not statistically significant. In all healthy women the endometrium showed homogeneous signal intensity in the sagittal T2-weighted images. In 12 of the 24 breast cancer patients, the endometrium showed inhomogeneous signal intensity. In 9 of 12 patients with an inhomogeneous endometrium with a thickness equal to or greater than 0.6 cm, histopathology confirmed polyps. In 3 patients endometrium hyperplasia was found. In one patient histopathology revealed a polyp and an endometrium carcinoma in stage T1 a N0. The endometrium carcinoma was not able to be seen via MR imaging. MR imaging might be helpful in the diagnosis of endometrium pathologies during tamoxifen therapy. Therefore, MR imaging of the pelvis could be used as a diagnostic tool in the follow-up diagnosis of the endometrium in breast cancer patients in tamoxifen therapy.

Combined MR direct thrombus imaging and non-contrast magnetic resonance venography reveal the evolution of deep vein thrombosis: a feasibility study.

PubMed

Mendichovszky, I A; Priest, A N; Bowden, D J; Hunter, S; Joubert, I; Hilborne, S; Graves, M J; Baglin, T; Lomas, D J

2017-06-01

Lower limb deep venous thrombosis (DVT) is a common condition with high morbidity and mortality. The aim of the study was to investigate the temporal evolution of the acute thrombus by magnetic resonance imaging (MRI) and its relationship to venous recanalization in patients with recurrent DVTs. Thirteen patients with newly diagnosed lower limb DVTs underwent MRI with non-contrast MR venography (NC-MRV) and MR direct thrombus imaging (MR-DTI), an inversion-recovery water-selective fast gradient-echo acquisition. Imaging was performed within 7 days of the acute thrombotic event, then at 3 and 6 months. By 3 months from the thrombotic event a third of the thrombi had resolved and by 6 months about half of the cases had resolved on the basis of vein recanalisation using NC-MRV. On the initial MR-DTI acute thrombus was clearly depicted by hyperintense signal, while the remaining thrombi were predominantly low signal at 3 and 6 months. Some residual thrombi contained small and fragmented persisting hyperintense areas at 3 months, clearing almost completely by 6 months. Our study suggests that synergistic venous assessment with combined NC-MRV and MR-DTI is able to distinguish acute venous thrombosis from the established (old) or evolving DVT detected by ultrasound. • MRI can distinguish between acute and evolving or chronic lower limb DVT • Two advanced MRI techniques can follow the evolution of lower limb DVT • MRI could be used to avoid an incorrect diagnosis of recurrent DVT • MRI could help avoid the risks and complications of lifelong anticoagulation therapy.

New developments in pediatric venous thromboembolism and anticoagulation, including the target-specific oral anticoagulants.

PubMed

Lyle, Courtney A; Sidonio, Robert F; Goldenberg, Neil A

2015-02-01

Pediatric venous thromboembolism (VTE) can affect children of all ages, requiring considerable pharmacologic intervention and is often associated with significant morbidity. Current research efforts are directed toward the development of risk-stratified VTE prevention strategies employing pharmacologic thromboprophylaxis, the optimization of conventional anticoagulation, and the investigation of the safety and efficacy of target-specific oral anticoagulants (TSOACs) in children. Recent research has considerably improved the understanding of risk factors of hospital-acquired VTE and how these factors may be employed in risk-stratified paradigms for VTE prevention in children. Additional insight has been gained in the optimization of conventional anticoagulants in special populations such as neonates and children with inflammatory conditions, and in improving the overall safety and compliance with periprocedural anticoagulation and the use of home International Normalized Ratio monitoring. Furthermore, the use of TSOACs has been described in children and is the focus of numerous ongoing clinical trials that are evaluating the safety and efficacy of these agents in children with VTE. Identification of hospital-acquired VTE risk factors may inform pediatric VTE prevention strategies. Although initial use of TSOACs may be promising, investigation of safety and efficacy in children is still underway.

Overview of a pharmacist anticoagulation certificate program.

PubMed

Kirk, Julienne K; Edwards, Rebecca; Brewer, Andrew; Miller, Cathey; Bray, Bryan; Groce, James B

2017-07-01

To describe the design of an ongoing anticoagulation certificate program and annual renewal update for pharmacists. Components of the anticoagulation certificate program include home study, pre- and posttest, live sessions, case discussions with evaluation and presentation, an implementation plan, and survey information (program evaluation and use in practice). Clinical reasoning skills were assessed through case work-up and evaluation prior to live presentation. An annual renewal program requires pharmacists to complete home study and case evaluations. A total of 361 pharmacists completed the anticoagulation certificate program between 2002 and 2015. Most (62%) practiced in ambulatory care and 38% in inpatient care settings (8% in both). In the past four years, 71% were working in or starting anticoagulation clinics in ambulatory and inpatient settings. In their evaluations of the program, an average of 90% of participants agreed or strongly agreed the lecture material was relevant and objectives were met. Pharmacists are able to apply knowledge and skills in management of anticoagulation. This structured practice-based continuing education program was intended to enhance pharmacy practice and has achieved that goal. The certificate program in anticoagulation was relevant to pharmacists who attended the program. Copyright © 2017. Published by Elsevier Inc.

Cross-cultural Adaptation of the Oral Anticoagulation Knowledge Test to the Brazilian Portuguese.

PubMed

Praxedes, Marcus Fernando da Silva; Abreu, Mauro Henrique Nogueira Guimarães; Ribeiro, Daniel Dias; Marcolino, Milena Soriano; Paiva, Saul Martins de; Martins, Maria Auxiliadora Parreiras

2017-05-01

Patients' knowledge about oral anticoagulant therapy may favor the achievement of therapeutic results and the prevention of adverse pharmacotherapy-related events. Brazil lacks validated instruments for assessing the patient's knowledge about treatment with warfarin. This study aimed to perform the cross-cultural adaptation of the Oral Anticoagulation Knowledge (OAK) Test instrument from English into Portuguese. This is a methodological study developed in an anticoagulation clinic of a public university hospital. The study included initial translation, synthesis of translations, back-translation, review by the experts committee and pre-testing with 30 individuals. We obtained semantic equivalence through the analysis of the referential and general meaning of each item. The conceptual equivalence of the items sought to demonstrate the relevance and acceptability of the instrument. The process of cross-cultural adaptation produced the final version of the OAK Test in Brazilian Portuguese entitled "Teste de Conhecimento sobre Anticoagulação Oral". There was a suitable semantic and conceptual equivalence between the adapted version and the original version, as well as an excellent acceptability of this instrument.

Targeted Prostate Thermal Therapy with Catheter-Based Ultrasound Devices and MR Thermal Monitoring

NASA Astrophysics Data System (ADS)

Diederich, Chris; Ross, Anthony; Kinsey, Adam; Nau, Will H.; Rieke, Viola; Butts Pauly, Kim; Sommer, Graham

2006-05-01

Catheter-based ultrasound devices have significant advantages for thermal therapy procedures, including potential for precise spatial and dynamic control of heating patterns to conform to targeted volumes. Interstitial and transurethral ultrasound applicators, with associated treatment strategies, were developed for thermal ablation of prostate combined with MR thermal monitoring. Four types of multielement transurethral applicators were devised, each with different levels of selectivity and intended therapeutic goals: sectored tubular transducer devices with fixed directional heating patterns; planar and lightly focused curvilinear devices with narrow heating patterns; and multi-sectored tubular devices capable of dynamic angular control without applicator movement. These devices are integrated with a 4 mm delivery catheter, incorporate an inflatable cooling balloon (10 mm OD) for positioning within the prostate and capable of rotation via an MR-compatible motor. Similarly, interstitial devices (2.4 mm OD) have been developed for percutaneous implantation with fixed directional heating patterns (e.g., 180 deg.). In vivo experiments in canine prostate (n=15) under MR temperature imaging were used to evaluate the heating technology and develop treatment strategies. MR thermal imaging in a 0.5 T interventional MRI was used to monitor temperature contours and thermal dose in multiple slices through the target volume. Sectored transurethral devices produce directional coagulation zones, extending 15-20 mm radial distance to the outer prostate capsule. The curvilinear applicator produces distinct 2-3 mm wide lesions, and with sequential rotation and modulated dwell time can precisely conform thermal ablation to selected areas or the entire prostate gland. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the gland in short treatment times without applicator manipulation. Interstitial implants with

Anticoagulant management in the cardiovascular setting.

PubMed

Verheugt, Freek W A

2012-02-01

Vitamin K antagonists have been used as oral anticoagulants (OACs) for over five decades, yet their use in real-world practice is problematic primarily because of their narrow therapeutic window, exacerbated by extensive food and drug interactions, necessitating regular coagulation monitoring and dose adjustment. Around half of patients receiving warfarin are within the therapeutic range, exposing them to the dangers of under-anticoagulation (i.e. thrombosis formation) or over-anticoagulation (i.e. bleeding). A new generation of OACs with improved pharmacology promises to revolutionize antithrombotic management. Rivaroxaban, apixaban (both oral direct Factor Xa inhibitors) and dabigatran (a direct thrombin inhibitor) all exhibit predictable anticoagulant responses and few drug-drug interactions and do not require routine coagulation monitoring. © 2011 The Author Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Needs and barriers to improve the collaboration in oral anticoagulant therapy: a qualitative study

PubMed Central

2011-01-01

Background Oral anticoagulant therapy (OAT) involves many health care disciplines. Even though collaboration between care professionals is assumed to improve the quality of OAT, very little research has been done into the practice of OAT management to arrange and manage the collaboration. This study aims to identify the problems in collaboration experienced by the care professionals involved, the solutions they proposed to improve collaboration, and the barriers they encountered to the implementation of these solutions. Methods In the Netherlands, intensive follow-up of OAT is provided by specialized anticoagulant clinics (ACs). Sixty-eight semi-structured face-to-face interviews were conducted with 103 professionals working at an AC. These semi-structured interviews were transcribed verbatim and analysed inductively. Wagner's chronic care model (CCM) and Cabana's framework for improvement were used to categorize the results. Results AC professionals experienced three main bottlenecks in collaboration: lack of knowledge (mostly of other professionals), lack of consensus on OAT, and limited information exchange between professionals. They mentioned several solutions to improve collaboration, especially solutions of CCM's decision support component (i.e. education, regular meetings, and agreements and protocols). Education is considered a prerequisite for the successful implementation of other proposed solutions such as developing a multidisciplinary protocol and changing the allocation of tasks. The potential of the health care organization to improve collaboration seemed to be underestimated by professionals. They experienced several barriers to the successful implementation of the proposed solutions. Most important barriers were the lack motivation of non-AC professionals and lack of time to establish collaboration. Conclusions This study revealed that the collaboration in OAT is limited by a lack of knowledge, a lack of consensus, and a limited information

[Cataract surgery under topical anesthesia with oral anticoagulants].

PubMed

Wirbelauer, C; Weller, A; Häberle, H; Pham, D T

2004-09-01

Approximately 14 % of cataract surgery patients receive blood-thinning agents. In a prospective study, the influence of oral anticoagulants on intraoperative and postoperative hemorrhages in patients undergoing cataract surgery in topical anesthesia was investigated. 128 patients presenting for cataract surgery under oral anticoagulation were included. The mean preoperative prothrombin time was 39 +/- 18 %. Most patients (81 %) continued their oral anticoagulation (prothrombin time 34 +/- 13 %). All surgeries were performed in topical anesthesia. In 9 patients (7 %) an ocular hemorrhagic event was observed. These were not sight-threatening and resorbed spontaneously within a few days. Only one patient (0.8 %) had a slight hemorrhage in the anterior chamber. There were no differences (P > 0.05) between patients with or without hemorrhagic complications in the postoperative visual acuity, the intraocular pressure, the prothrombin time or the discontinuation of oral anticoagulants. Cataract surgery in topical anesthesia under oral anticoagulation did not increase the risk of sight-threatening hemorrhages. The continuation of oral anticoagulation seems particularly indicated for ambulatory cataract surgery.

Assessing Bleeding Risk in Patients Taking Anticoagulants

PubMed Central

Shoeb, Marwa; Fang, Margaret C.

2013-01-01

Anticoagulant medications are commonly used for the prevention and treatment of thromboembolism. Although highly effective, they are also associated with significant bleeding risks. Numerous individual clinical factors have been linked to an increased risk of hemorrhage, including older age, anemia, and renal disease. To help quantify hemorrhage risk for individual patients, a number of clinical risk prediction tools have been developed. These risk prediction tools differ in how they were derived and how they identify and weight individual risk factors. At present, their ability to effective predict anticoagulant-associated hemorrhage remains modest. Use of risk prediction tools to estimate bleeding in clinical practice is most influential when applied to patients at the lower spectrum of thromboembolic risk, when the risk of hemorrhage will more strongly affect clinical decisions about anticoagulation. Using risk tools may also help counsel and inform patients about their potential risk for hemorrhage while on anticoagulants, and can identify patients who might benefit from more careful management of anticoagulation. PMID:23479259

Initial investigation of a novel noninvasive weight loss therapy using MRI-Guided high intensity focused ultrasound (MR-HIFU) of visceral fat.

PubMed

Winter, Patrick M; Lanier, Matthew; Partanen, Ari; Dumoulin, Charles

2016-07-01

MRI-guided high intensity focused ultrasound (MR-HIFU) allows noninvasive heating of deep tissues. Specifically targeting visceral fat deposits with MR-HIFU could offer an effective therapy for reversing the development of obesity, diabetes, and metabolic syndrome. Overweight rats received either MR-HIFU of visceral fat, sham treatment, no treatment, or ex vivo temperature calibration. Conventional MR thermometry methods are not effective in fat tissue. Therefore, the T2 of fat was used to estimate heating in adipose tissue. HIFU treated rats lost 7.5% of their body weight 10 days after HIFU, compared with 1.9% weight loss in sham animals (P = 0.008) and 1.3% weight increase in untreated animals (P = 0.004). Additionally, the abdominal fat volume in treated animals decreased by 8.2 mL 7 days after treatment (P = 0.002). The T2 of fat at 1.5 Tesla increased by 3.3 ms per °C. The fat T2 was 103.3 ms before HIFU, but increased to 128.7 ms (P = 0.0005) after HIFU at 70 watts for 16 s and to 131.9 ms (P = 0.0005) after HIFU at 100 watts for 16 s. These experiments demonstrate that MR-HIFU of visceral fat could provide a safe, effective, and noninvasive weight loss therapy for combating obesity and the subsequent medical complications. Magn Reson Med 76:282-289, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

[Analysis on long-term compliance of anticoagulation treatment and demands of disease management in patients with atrial fibrillation].

PubMed

Zuo, Hui-juan; Su, Jiang-lian; Lin, Yun; Zeng, Zhe-chun; Wang, Jin-wen

2010-08-24

To analyze the long-term compliance of oral anticoagulant therapy and the demands of disease management in patient with atrial fibrillation (AF). Inpatients with AF taking warfarin were collected from Department of Internal Medicine from January 1 to December 31, 2008. Inpatients from departments of surgery, ophthalmology, otorhinolaryngology, dermatology and pediatrics and those on a previous warfarin therapy were excluded. The data of patient profiles, medical history and anticoagulant treatment were collected from electronic medical record. And the status of anticoagulant treatment one year later and demands of disease management were inquired by telephone. A total of 268 AF patients received a telephone survey. Among them, 145 patients (54.1%) continued taking warfarin. Gender, age, type of AF, duration of AF and history of ischemic stroke was not significantly associated with the compliance of anticoagulant treatment. The odds ratio was 1.74 (95%CI: 0.67-4.47), 0.87 (95%CI: 0.30-2.53), 1.59 (95%CI: 0.35-1.09), 1.09 (95%CI: 0.61-1.93) and 0.44 (95%CI: 0.12-1.60) respectively. Among patients on warfarin, INR was monitored monthly in 88 patients (60.7%) and 70 patients (48.3%) had an INR value of 2.0-3.0. Among 123 withdrawal patients, 88 patients (71.5%) terminated treatment within 6 month. The common reasons included patient ignorance about long-term anticoagulant treatment (35.0%) and switching to aspirin because of a poor effect (24.4%). About 80% of patients wished to obtain instructions about INR monitoring and adjustment of drug dosage. Among them, 196/268 patients (73.1%) wished for a regular follow-up. And 176/196 patients (89.8%) opted for a telephone follow-up and 150/176 patients (85.2%) wanted to receive monthly instructions. The compliance of anticoagulation treatment and the target-meeting proportion of INR value are relative low. And the common reasons of withdrawal are patient ignorance about long-term anticoagulant treatment and switching to

MARINE LEECH ANTICOAGULANT DIVERSITY AND EVOLUTION.

PubMed

Tessler, Michael; Marancik, David; Champagne, Donald; Dove, Alistair; Camus, Alvin; Siddall, Mark E; Kvist, Sebastian

2018-03-16

Leeches (Annelida: Hirudinea) possess powerful salivary anticoagulants and, accordingly, are frequently employed in modern, authoritative medicine. Members of the almost exclusively marine family Piscicolidae account for 20% of leech species diversity, and feed on host groups (e.g., sharks) not encountered by their freshwater and terrestrial counterparts. Moreover, some species of Ozobranchidae feed on endangered marine turtles and have been implicated as potential vectors for the tumor-associated turtle herpesvirus. In spite of their ecological importance and unique host associations, there is a distinct paucity of data regarding the salivary transcriptomes of either of these families. Using next generation sequencing, we profiled transcribed, putative anticoagulants and other salivary bioactive compounds that have previously been linked to bloodfeeding from 7 piscicolid species (3 elasmobranch-feeders; 4 non-cartilaginous fish-feeders) and 1 ozobranchid species (2 samples). In total, 149 putative anticoagulants and bioactive loci were discovered in varying constellations throughout the different samples. The putative anticoagulants showed a broad spectrum of described antagonistic pathways, such as inhibition of factor Xa and platelet aggregation, that likely have similar bioactive roles in marine fish and turtles. A transcript with homology to ohanin, originally isolated from king cobras, was found in Cystobranchus vividus but is otherwise unknown from leeches. Estimation of selection pressures for the putative anticoagulants recovered evidence for both positive and purifying selection along several isolated branches in the gene trees and positive selection was also estimated for a few select codons in a variety of marine species. Similarly, phylogenetic analyses of the amino acid sequences for several anticoagulants indicated divergent evolution.

Recent progress and market analysis of anticoagulant drugs

PubMed Central

Fan, Ping; Gao, Yangyang; Zheng, Minglin; Xu, Ting; Schoenhagen, Paul

2018-01-01

This review describes epidemiology of thromboembolic disease in China and abroad, evaluates trends in the development of anticoagulant drugs, and analyzes the market situation based on large amounts of accumulated data. Specifically, we describe advances in clinical application of anticoagulants and analyze the most commonly used anticoagulants in the market systematically.

Using 3D dosimetry to quantify the Electron Return Effect (ERE) for MR-image-guided radiation therapy (MR-IGRT) applications

NASA Astrophysics Data System (ADS)

Lee, Hannah J.; Choi, Gye Won; Alqathami, Mamdooh; Kadbi, Mo; Ibbott, Geoffrey

2017-05-01

Image-guided radiation therapy (IGRT) using computed tomography (CT), cone-beam CT, MV on-board imager (OBI), and kV OBI systems have allowed for more accurate patient positioning prior to each treatment fraction. While these imaging modalities provide excellent bony anatomy image quality, MRI surpasses them in soft tissue image contrast for better visualization and tracking of soft tissue tumors with no additional radiation dose to the patient. A pre-clinical integrated 1.5 T magnetic resonance imaging and 7 MV linear accelerator system (MR-linac) allows for real-time tracking of soft tissues and adaptive treatment planning prior to each treatment fraction. However, due to the presence of a strong magnetic field from the MR component, there is a three dimensional (3D) change in dose deposited by the secondary electrons. Especially at nonhomogeneous anatomical sites with tissues of very different densities, dose enhancements and reductions can occur due to the Lorentz force influencing the trajectories of secondary electrons. These dose changes at tissue interfaces are called the electron return effect or ERE. This study investigated the ERE using 3D dosimeters.

A framework for the correction of slow physiological drifts during MR-guided HIFU therapies: Proof of concept.

PubMed

Zachiu, Cornel; Denis de Senneville, Baudouin; Moonen, Chrit; Ries, Mario

2015-07-01

While respiratory motion compensation for magnetic resonance (MR)-guided high intensity focused ultrasound (HIFU) interventions has been extensively studied, the influence of slow physiological motion due to, for example, peristaltic activity, has so far been largely neglected. During lengthy interventions, the magnitude of the latter can exceed acceptable therapeutic margins. The goal of the present study is to exploit the episodic workflow of these therapies to implement a motion correction strategy for slow varying drifts of the target area and organs at risk over the entire duration of the intervention. The therapeutic workflow of a MR-guided HIFU intervention is in practice often episodic: Bursts of energy delivery are interleaved with periods of inactivity, allowing the effects of the beam on healthy tissues to recede and/or during which the plan of the intervention is reoptimized. These periods usually last for at least several minutes. It is at this time scale that organ drifts due to slow physiological motion become significant. In order to capture these drifts, the authors propose the integration of 3D MR scans in the therapy workflow during the inactivity intervals. Displacements were estimated using an optical flow algorithm applied on the 3D acquired images. A preliminary study was conducted on ten healthy volunteers. For each volunteer, 3D MR images of the abdomen were acquired at regular intervals of 10 min over a total duration of 80 min. Motion analysis was restricted to the liver and kidneys. For validating the compatibility of the proposed motion correction strategy with the workflow of a MR-guided HIFU therapy, an in vivo experiment on a porcine liver was conducted. A volumetric HIFU ablation was completed over a time span of 2 h. A 3D image was acquired before the first sonication, as well as after each sonication. Following the volunteer study, drifts larger than 8 mm for the liver and 5 mm for the kidneys prove that slow physiological motion

A framework for the correction of slow physiological drifts during MR-guided HIFU therapies: Proof of concept

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zachiu, Cornel, E-mail: C.Zachiu@umcutrecht.nl; Moonen, Chrit; Ries, Mario

Purpose: While respiratory motion compensation for magnetic resonance (MR)-guided high intensity focused ultrasound (HIFU) interventions has been extensively studied, the influence of slow physiological motion due to, for example, peristaltic activity, has so far been largely neglected. During lengthy interventions, the magnitude of the latter can exceed acceptable therapeutic margins. The goal of the present study is to exploit the episodic workflow of these therapies to implement a motion correction strategy for slow varying drifts of the target area and organs at risk over the entire duration of the intervention. Methods: The therapeutic workflow of a MR-guided HIFU intervention ismore » in practice often episodic: Bursts of energy delivery are interleaved with periods of inactivity, allowing the effects of the beam on healthy tissues to recede and/or during which the plan of the intervention is reoptimized. These periods usually last for at least several minutes. It is at this time scale that organ drifts due to slow physiological motion become significant. In order to capture these drifts, the authors propose the integration of 3D MR scans in the therapy workflow during the inactivity intervals. Displacements were estimated using an optical flow algorithm applied on the 3D acquired images. A preliminary study was conducted on ten healthy volunteers. For each volunteer, 3D MR images of the abdomen were acquired at regular intervals of 10 min over a total duration of 80 min. Motion analysis was restricted to the liver and kidneys. For validating the compatibility of the proposed motion correction strategy with the workflow of a MR-guided HIFU therapy, an in vivo experiment on a porcine liver was conducted. A volumetric HIFU ablation was completed over a time span of 2 h. A 3D image was acquired before the first sonication, as well as after each sonication. Results: Following the volunteer study, drifts larger than 8 mm for the liver and 5 mm for the kidneys

Major bleeding complications in patients treated with direct oral anticoagulants: One-year observational study in a Paris Hospital.

PubMed

Deville, L; Konan, M; Hij, A; Goldwirt, L; Peyrony, O; Fieux, F; Faure, P; Madelaine, I; Villiers, S; Farge-Bancel, D; Frère, C

Direct oral anticoagulants (DAOC) are indicated for the treatment of venous thromboembolism and the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. Given their advantages and friendly use for patient, the prescription of long term DOAC therapy has rapidly increased both as first line treatment while initiating anticoagulation and as a substitute to vitamins K antagonist (VKA) in poorly controlled patients. However, DOAC therapy can also be associated with significant bleeding complications, and in the absence of specific antidote at disposal, treatment of serious hemorrhagic complications under DOAC remains complex. We report and discuss herein five cases of major hemorrhagic complications under DOAC, which were reported to the pharmacological surveillance department over one year at Saint-Louis University Hospital (Paris, France). We further discuss the need for careful assessment of the risk/benefit ratio at time of starting DOAC therapy in daily clinical practice. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Anticoagulation by factor Xa inhibitors.

PubMed

Orfeo, T; Butenas, S; Brummel-Ziedins, K E; Gissel, M; Mann, K G

2010-08-01

Therapeutic agents that regulate blood coagulation are critical to the management of thrombotic disorders, with the selective targeting of factor (F) Xa emerging as a promising approach. To assess anticoagulant strategies targeting FXa. A deterministic computational model of tissue factor (Tf)-initiated thrombin generation and two empirical experimental systems (a synthetic coagulation proteome reconstruction using purified proteins and a whole blood model) were used to evaluate clinically relevant examples of the two available types of FXa-directed anticoagulants [an antithrombin (AT)-dependent agent, fondaparinux, and an AT-independent inhibitor, Rivaroxaban] in experimental regimens relevant to long-term (suppression of new Tf-initiated events) and acute (suppression of ongoing coagulation processes) clinical applications. Computational representations of each anticoagulant's efficacy in suppressing thrombin generation over a range of anticoagulant concentrations in both anticoagulation regimens were validated by results from corresponding empirical reconstructions and were consistent with those recommended for long-term and acute clinical applications, respectively. All three model systems suggested that Rivaroxaban would prove more effective in the suppression of an ongoing coagulation process than fondaparinux, reflecting its much higher reactivity toward the prothrombinase complex. The success of fondaparinux in acute settings in vivo is not explained solely by its properties as an FXa inhibitor. We have reported that FIXa contributes to the long-term capacity of clot-associated catalysts to restart a coagulation process, suggesting that the enhanced anti-FIXa activity of fondaparinux-AT may be critical to its success in acute settings in vivo. © 2010 International Society on Thrombosis and Haemostasis.

Quality of Vitamin K Antagonist Anticoagulation in Spain: Prevalence of Poor Control and Associated Factors.

PubMed

Anguita Sánchez, Manuel; Bertomeu Martínez, Vicente; Cequier Fillat, Ángel

2015-09-01

To study the prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain in patients with nonvalvular atrial fibrillation, and to identify associated factors. We studied 1056 consecutive patients seen at 120 cardiology clinics in Spain between November 2013 and March 2014. We analyzed the international normalized ratio from the 6 months prior to the patient's visit, calculating the prevalence of poorly controlled anticoagulation, defined as < 65% time in therapeutic range using the Rosendaal method. Mean age was 73.6 years (standard deviation, 9.8 years); women accounted for 42% of patients. The prevalence of poorly controlled anticoagulation was 47.3%. Mean time in therapeutic range was 63.8% (25.9%). The following factors were independently associated with poorly controlled anticoagulation: kidney disease (odds ratio = 1.53; 95% confidence interval, 1.08-2.18; P = .018), routine nonsteroidal anti-inflammatory drugs (odds ratio = 1.79; 95% confidence interval, 1.20-2.79; P = .004), antiplatelet therapy (odds ratio = 2.16; 95% confidence interval, 1.49-3.12; P < .0001) and absence of angiotensin receptor blockers (odds ratio = 1.39; 95% confidence interval, 1.08-1.79; P = .011). There is a high prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain. Factors associated with poor control are kidney disease, routine nonsteroidal anti-inflammatory drugs, antiplatelet use, and absence of angiotensin receptor blockers. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

[Prophylaxis of thromboembolism in atrial fibrillation: new oral anticoagulants and left atrial appendage closure].

PubMed

Zeus, Tobias; Kelm, Malte; Bode, Christoph

2015-08-01

Thrombo-embolic prophylaxis is a key element within the therapy of atrial fibrillation/atrial flutter. Besides new oral anticoagulants the concept of left atrial appendage occlusion has approved to be a good alternative option, especially in patients with increased risk of bleeding. © Georg Thieme Verlag KG Stuttgart · New York.

CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study.

PubMed

Caraco, Y; Blotnick, S; Muszkat, M

2008-03-01

Warfarin anticoagulation effect is characterized by marked variability, some of which has been attributed to CYP2C9 polymorphisms. This study prospectively examines whether a priori knowledge of CYP2C9 genotype may improve warfarin therapy. Patients were randomly assigned to receive warfarin by a validated algorithm ("control", 96 patients) or CYP2C9 genotype-adjusted algorithms ("study", 95 patients). The first therapeutic international normalized ratio and stable anticoagulation were reached 2.73 and 18.1 days earlier in the study group, respectively (P<0.001). The faster rate of initial anticoagulation was driven by a 28% higher daily dose in the study group (P<0.001). Study group patients spent more time within the therapeutic range (80.4 vs 63.4%, respectively, P<0.001) and experienced less minor bleeding (3.2 vs 12.5%, P<0.02, respectively). In conclusion, CYP2C9 genotype-guided warfarin therapy is more efficient and safer than the "average-dose" protocol. Future research should focus on construction of algorithms that incorporate other polymorphisms (VKORC1), host factors, and environmental influences.

Risk of long-term anticoagulation under sustained severe arterial hypertension: A translational study comparing warfarin and the new oral anticoagulant apixaban

PubMed Central

Pfeilschifter, Waltraud; Steinstraesser, Thurid; Paulus, Patrick; Zeiner, Pia Susan; Bohmann, Ferdinand; Theisen, Alf; Lindhoff-Last, Edelgard; Penski, Cornelia; Wagner, Marlies; Mittelbronn, Michel

2016-01-01

New oral anticoagulants for the prevention of stroke and systemic embolism in patients with atrial fibrillation have recently been introduced. In this translational study, we explored the risk of long-term anticoagulation on intracerebral hemorrhage under sustained severe arterial hypertension. We initiated anticoagulation with warfarin or apixaban in spontaneously hypertensive rats prone to develop severe hypertension and subsequent intracerebral bleeding complications. A non-anticoagulated group served as control. During an 11-week-study period, blood pressure, anticoagulation parameters, and clinical status were determined regularly. The incidence of histopathologically proven intracerebral hemorrhage was defined as the primary endpoint. Both warfarin and apixaban anticoagulation was fairly stable during the study period, and all rats developed severe hypertension. Intracerebral hemorrhage was determined in 29% (4/14) of warfarin rats and in 10% (1/10) of apixaban rats. Controls did not show cerebral bleeding complications (chi-square not significant). Mortality rate at study termination was 33% (2/6) in controls, 43% (6/14) in the warfarin group, and 60% (6/10) in the apixaban group. Animals died from extracerebral complications in most cases. Our study describes an experimental intracerebral hemorrhage model in the context of sustained hypertension and long-term anticoagulation. Extracerebral bleeding complications occurred more often in warfarin-treated animals compared with apixaban and control rats. PMID:27189904

Failure mode and effects analysis to reduce risk of anticoagulation levels above the target range during concurrent antimicrobial therapy.

PubMed

Daniels, Lisa M; Barreto, Jason N; Kuth, John C; Anderson, Jeremy R; Zhang, Beilei; Majka, Andrew J; Morgenthaler, Timothy I; Tosh, Pritish K

2015-07-15

A failure mode and effects analysis (FMEA) was conducted to analyze the clinical and operational processes leading to above-target International Normalized Ratios (INRs) in warfarin-treated patients receiving concurrent antimicrobial therapy. The INRs of patients on long-term warfarin therapy who received a course of trimethoprim-sulfamethoxazole, metronidazole, fluconazole, miconazole, or voriconazole (highly potentiating antimicrobials, or HPAs) between September 1 and December 31, 2011, were compared with patients on long-term warfarin therapy who did not receive any antimicrobial during the same period. A multidisciplinary team of physicians, pharmacists, and a systems analyst was then formed to complete a step-by-step outline of the processes involved in warfarin management and concomitant HPA therapy, followed by an FMEA. Patients taking trimethoprim-sulfamethoxazole, metronidazole, or fluconazole demonstrated a significantly increased risk of having an INR of >4.5. The FMEA identified 134 failure modes. The most common failure modes were as follows: (1) electronic medical records did not identify all patients receiving warfarin, (2) HPA prescribers were unaware of recommended warfarin therapy when HPAs were prescribed, (3) HPA prescribers were unaware that a patient was taking warfarin and that the drug interaction is significant, and (4) warfarin managers were unaware that an HPA had been prescribed for a patient. An FMEA determined that the risk of adverse events caused by concomitantly administering warfarin and HPAs can be decreased by preemptively identifying patients receiving warfarin, having a care process in place, alerting providers about the patient's risk status, and notifying providers at the anticoagulation clinic. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Optimal duration of anticoagulation in patients with venous thromboembolism

PubMed Central

Prandoni, Paolo; Piovella, Chiara; Spiezia, Luca; Valle, Fabio Dalla; Pesavento, Raffaele

2011-01-01

The risk of recurrent venous thromboembolism (VTE) approaches 40 per cent of all patients after 10 yr of follow up. This risk is higher in patients with permanent risk factors of thrombosis such as active cancer, prolonged immobilization from medical diseases, and antiphospholipid syndrome; in carriers of several thrombophilic abnormalities, including deficiencies of natural anticoagulants; and in patients with unprovoked presentation. Patients with permanent risk factors of thrombosis should receive indefinite anticoagulation, consisting of subtherapeutic doses of low molecular weight heparin in cancer patients, and oral anticoagulants in all other conditions. Patients whose VTE is triggered by major surgery or trauma should be offered three months of anticoagulation. Patients with unprovoked VTE, including carriers of thrombophilia, and those whose thrombotic event is associated with minor risk factors (such as hormonal treatment, minor injuries, long travel) should receive at least three months of anticoagulation. The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk. Post-baseline variables, such as the D-dimer determination and the ultrasound assessment of residual thrombosis can help identify those patients in whom anticoagulation can be safely discontinued. As a few emerging anti-Xa and anti-IIa compounds seem to induce fewer haemorrhagic complications than conventional anticoagulation, while preserving at least the same effectiveness, these have the potential to open new scenarios for decisions regarding the duration of anticoagulation in patients with VTE. PMID:21808129

Optimal duration of anticoagulation in patients with venous thromboembolism.

PubMed

Prandoni, Paolo; Piovella, Chiara; Spiezia, Luca; Dalla Valle, Fabio; Pesavento, Raffaele

2011-07-01

The risk of recurrent venous thromboembolism (VTE) approaches 40 per cent of all patients after 10 yr of follow up. This risk is higher in patients with permanent risk factors of thrombosis such as active cancer, prolonged immobilization from medical diseases, and antiphospholipid syndrome; in carriers of several thrombophilic abnormalities, including deficiencies of natural anticoagulants; and in patients with unprovoked presentation. Patients with permanent risk factors of thrombosis should receive indefinite anticoagulation, consisting of subtherapeutic doses of low molecular weight heparin in cancer patients, and oral anticoagulants in all other conditions. Patients whose VTE is triggered by major surgery or trauma should be offered three months of anticoagulation. Patients with unprovoked VTE, including carriers of thrombophilia, and those whose thrombotic event is associated with minor risk factors (such as hormonal treatment, minor injuries, long travel) should receive at least three months of anticoagulation. The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk. Post-baseline variables, such as the D-dimer determination and the ultrasound assessment of residual thrombosis can help identify those patients in whom anticoagulation can be safely discontinued. As a few emerging anti-Xa and anti-IIa compounds seem to induce fewer haemorrhagic complications than conventional anticoagulation, while preserving at least the same effectiveness, these have the potential to open new scenarios for decisions regarding the duration of anticoagulation in patients with VTE.

Oral and parenteral anticoagulants: new kids on the block.

PubMed

Aditya, S

2012-01-01

Well-documented drawbacks of traditional anticoagulants have lead to the quest for an ideal anticoagulant resulting in a surge of novel anticoagulant molecules. These newer agents directly target specific steps in coagulation cascade and include newer low molecular weight heparins (adomiparin), ultra low molecular weight heparins (semuloparin, RO-14), inhibitors of activated factor II (dabigatran, AZD0837), X (rivaroxaban, apixaban, edoxaban, betrixaban), IX (REG1,2), XI (antisense oligonucleotides, BMS 262084, clavatadine A), VII/tissue factor (tifacogin, PCI 274836, and BMS 593214), V (recomodulin, solulin), VIII (TB402), dual thrombin/factor X inhibitors (EP21709, tanogitran), and newer vitamin K antagonists (tecarfarin). Direct thrombin inhibitors and Factor X inhibitors are the most clinically advanced. This article discusses the recent advances in the development of novel targets of anticoagulants. Medline, EMBASE, cochrane database, medscape, SCOPUS, and clinicaltrials.gov were searched using terms "anticoagulants", "blood coagulation inhibitors", "anticoagulants and venous thromboembolism", "anticoagulants and atrial fibrillation", and "'antithrombins." Journal articles published from 2007 to 2012 discussing pharmacology and/or clinical trials were screened.

Status of oral anticoagulant treatment in patients with nonvalvular atrial fibrillation in Spain. REACT-AF Study.

PubMed

de Andrés-Nogales, F; Oyagüez, I; Betegón-Nicolás, L; Canal-Fontcuberta, C; Soto-Álvarez, J

2015-03-01

Oral anticoagulant therapy is complex due to the need for control and the hemorrhagic risk the therapy entails. This study aims to determine the standard clinical practice in the treatment for preventing stroke in patients with nonvalvular atrial fibrillation (NVAF) in Spain. The Real Evidence of Anti Coagulation Treatment in AF is a European, multicenter, multinational, observational, retrospectively monitored cohort of patients with NVAF. This study included patients recruited in Spain with at least one visit during the period of inclusion (May 2010/April 2012). The study evaluated the following: a) persistence of oral anticoagulant treatment (time to discontinuation); b) persistence rate (% of patients in treatment) at 6, 12 and 24 months and at 5 years; c) therapeutic compliance (medication possession ratio); d) the correlation between the treatment followed and that recommended by the European Society of Cardiology; and the incidence of stroke and hemorrhagic events. The patients treated with oral anticoagulants (n=7,526) had a median time to discontinuation of treatment of 1.99 years and a persistence rate at 5 years of 26% (discontinuation ≥3 months). The compliance (mean MPR) was 0.54±0.36. The incidence of stroke was 0.3/100 person-years, and the incidence of hemorrhagic events was 2.4/100 person-years. Fifty-eight percent of the patients with NVAF (n=12,514) followed the recommendations of the European Society of Cardiology. Forty-two percent of the patients with NVAF did not follow the recommendations of the European Society of Cardiology. We detected low persistence and treatment compliance rates for oral anticoagulants. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Short-Term Anticoagulant Therapy and Thrombus Location Are Independent Risk Factors for Delayed Recanalization of Deep Vein Thrombosis.

PubMed

Zhang, Chuanlin; Fu, Qining; Zhao, Yu; Mu, Shaoyu; Liu, Liping

2016-01-21

Prompt recanalization of the vein containing the thrombus is an important goal during the initial treatment of DVT, and risk factors for delayed recanalization in patients with deep vein thrombosis (DVT) in the lower extremities need to be determined. A total of 174 patients with DVT in lower extremities were recruited from June 2014 to March 2015 at our hospital. Duplex ultrasound scanning was conducted for all patients at 1 and 6 months after baseline evaluation. We divided the patients into recanalization and non-recanalization groups and analyzed risk factors for delayed recanalization. The univariate analysis revealed that an oral anticoagulant time of less than 3 months and venous thrombus location were risk factors for delayed recanalization (P<0.01). However, age, gender, hypertension, diabetes, pulmonary embolism, incidence factors, the use of catheter-directed thrombolytic (CDT) drugs, and inferior vena cava filter (IVCF) implantation had no influence on the incidence of delayed recanalization in patients with DVT (P>0.05). The multivariate analysis showed that patients with an anticoagulant time of less than 3 months had a lower incidence of recanalization than those with an anticoagulant time of more than 3 months (OR=2.358, P<0.05). The risk of delayed recanalization in patients with proximal DVT was 7 times higher than that in patients with distal DVT. Duration of anticoagulant treatment of less than 3 months and venous thrombus location are independent risk factors for delayed recanalization of DVT in the lower extremities.

Intravenous lipid emulsion does not reverse dabigatran-induced anticoagulation in a rat model.

PubMed

Blum, Jared; Carreiro, Stephanie; Hack, Jason B

2013-10-01

The anticoagulant dabigatran has no reversal agent and may cause life-threatening bleeding in patients with trauma or closed-space hemorrhage. Intravenous lipid emulsion (ILE) is thought to create a lipid compartment in serum that sequesters lipophilic drugs. Dabigatran is lipophilic, and its anticoagulant effects are concentration dependent. The study objective was to determine if ILE therapy reverses dabigatran's anticoagulant effects. Twenty rats were selected at random, 10 in the ILE group and 10 in a normal saline (NS) control group. Animals had a baseline tail bleeding time (T0), followed by oral dabigatran administration (15 mg/kg). At 45 minutes (T45), a second tail bleed time measurement was performed, followed by a 7-minute infusion of 15 mL/kg ILE or NS. A final 60-minute (T60) bleed time measurement was obtained. An ILE-only group of five animals had bleeding times assessed prior to (T0) and 15 minutes after (T15) ILE therapy. A mixed-effect repeated-measures analysis of variance modeling the effect of time, group, and the interaction of group and time on bleed times was conducted. There was a significant within-subject change in bleeding time across the assessment points (F(2,36) = 33; p < 0.001), but there were no effect of group (F(1,18) = 1.42, p = 0.25) or an interaction between group and assessment point on mean bleeding time (F(2,36) = 0.59, p = 56). Between T0 and T45, average bleeding times increased from 109.5 seconds (95% confidence interval [CI] = 94 to 125 seconds) to 231.8 seconds (95% CI = 193 to 271 seconds; p < 0.0001) for both the ILE group and the NS control group. Between T45 and T60, bleeding times in the ILE group decreased by 31.5 seconds (95% CI = -77 to 14 seconds) and by 6 seconds (95% CI = -67 to 55 seconds) in the NS group (p = 0.46). In the five ILE-only animals, the average bleeding time at T0 was 114 seconds (95% CI = 62 to 166 seconds), which increased significantly at T15 to 237�

Atrial Fibrillation, Type 2 Diabetes, and Non-Vitamin K Antagonist Oral Anticoagulants: A Review.

PubMed

Plitt, Anna; McGuire, Darren K; Giugliano, Robert P

2017-04-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a 5-fold increase in the risk for stroke. Type 2 diabetes is an independent risk factor for both stroke and atrial fibrillation, and in the setting of AF, type 2 diabetes is independently associated with a 2% to 3.5% increase in absolute stroke rate per year. The overlap in the pathophysiologies of AF and type 2 diabetes are not well understood, and current practice guidelines provide few recommendations regarding patients with both conditions. In this article, we review the epidemiology and pathophysiology of the nexus of AF and type 2 diabetes. Furthermore, we analyze the subgroup of patients with type 2 diabetes enrolled in phase 3 clinical trials of non-vitamin K antagonist oral anticoagulants in prevention of arterial thromboembolism in AF, highlighting the greater absolute benefit of non-vitamin K oral anticoagulants in patients with type 2 diabetes. Finally, we offer recommendations on risk stratification and therapy for patients with concomitant AF and type 2 diabetes. We highlight the increased thromboembolic risk with coexisting AF and type 2 diabetes. We recommend that further studies be done to evaluate the potential benefits of anticoagulation for all patients who have both and the potential for non-vitamin K oral anticoagulants to have greater benefits than risks over vitamin K antagonists.

Assessment of psychometric properties of the Brazilian version of the oral anticoagulation knowledge test.

PubMed

Praxedes, Marcus Fernando da Silva; de Abreu, Mauro Henrique Nogueira Guimarães; Paiva, Saul Martins; Mambrini, Juliana Vaz de Melo; Marcolino, Milena Soriano; Martins, Maria Auxiliadora Parreiras

2016-06-24

The aim of this study was to evaluate the psychometric properties of the Brazilian version of the Oral Anticoagulation Knowledge (OAK) Test. This study, conducted in an anticoagulation clinic, included 201 Brazilian participants aged over 18 years, who had been using warfarin for more than two months. The reliability of the instrument was evaluated by assessing internal consistency (Kuder-Richardson coefficient) and reproducibility (test-retest reliability). The validity was evaluated by hypothesizing that there would be a positive correlation of moderate to strong intensity between the correctness levels of the OAK Test and time within therapeutic range (TTR) values, which is a measure used to evaluate the quality of oral anticoagulation. The instrument exhibited good psychometric properties. The total a Kuder-Richardson coefficient value was 0.818 and intraclass correlation coefficient was 0.967. The validity revealed a strong positive correlation between the values of the level of knowledge, as measured by the OAK Test and the TTR values (rs = 0.780). The instrument proved to be a reliable and valid tool for evaluating the knowledge of Brazilian patients on oral anticoagulation therapy with warfarin. This instrument may be incorporated into the practice of health care for substantiating the structuring of educational activities to ensure the improvement of knowledge about the use of warfarin, thereby increasing the effectiveness and safety of treatment.

Survey of Botulinum Toxin Injections in Anticoagulated Patients: Korean Physiatrists' Preference in Controlling Anticoagulation Profile Prior to Intramuscular Injection.

PubMed

Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P; Ismail, Farooq; Im, Sun

2016-04-01

To evaluate Korean physiatrists' practice of performing intramuscular botulinum toxin injection in anticoagulated patients and to assess their preference in controlling the bleeding risk before injection. As part of an international collaboration survey study, a questionnaire survey was administered to 100 Korean physiatrists. Physiatrists were asked about their level of experience with botulinum toxin injection, the safe international normalized ratio range in anticoagulated patients undergoing injection, their tendency for injecting into deep muscles, and their experience of bleeding complications. International normalized ratio <2.0 was perceived as an ideal range for performing Botulinum toxin injection by 41% of the respondents. Thirty-six respondents replied that the international normalized ratio should be lowered to sub-therapeutic levels before injection, and 18% of the respondents reported that anticoagulants should be intentionally withheld and discontinued prior to injection. In addition, 20%-30% of the respondents answered that they were uncertain whether they should perform the injection regardless of the international normalized ratio values. About 69% of the respondents replied that they did have any standardized protocols for performing botulinum toxin injection in patients using anticoagulants. Only 1 physiatrist replied that he had encountered a case of compartment syndrome. In accordance with the lack of consensus in performing intramuscular botulinum toxin injection in anticoagulated patients, our survey shows a wide range of practices among many Korean physiatrists; they tend to avoid botulinum toxin injection in anticoagulated patients and are uncertain about how to approach these patients. The results of this study emphasize the need for formulating a proper international consensus on botulinum toxin injection management in anticoagulated patients.

Aligning health care policy with evidence-based medicine: the case for funding direct oral anticoagulants in atrial fibrillation.

PubMed

Stone, James A; Earl, Karen M; O'Neill, Blair J; Sharma, Mukul; Huynh, Thao; Leblanc, Kori; Ward, Richard; Teal, Philip A; Cox, Jafna L

2014-10-01

Misalignment between evidence-informed clinical care guideline recommendations and reimbursement policy has created care gaps that lead to suboptimal outcomes for patients denied access to guideline-based therapies. The purpose of this article is to make the case for addressing this growing access barrier to optimal care. Stroke prevention in atrial fibrillation (AF) is discussed as an example. Stroke is an extremely costly disease, imposing a significant human, societal, and economic burden. Stroke in the setting of AF carries an 80% probability of death or disability. Although two-thirds of these strokes are preventable with appropriate anticoagulation, this has historically been underprescribed and poorly managed. National and international guidelines endorse the direct oral anticoagulants as first-line therapy for this indication. However, no Canadian province has provided these agents with an unrestricted listing. These decisions appear to be founded on silo-based cost assessment-the drug costs rather than the total system costs-and thus overlook several important cost-drivers in stroke. The discordance between best scientific evidence and public policy requires health care providers to use a potentially suboptimal therapy in contravention of guideline recommendations. It represents a significant obstacle for knowledge translation efforts that aim to increase the appropriate anticoagulation of Canadians with AF. As health care professionals, we have a responsibility to our patients to engage with policy-makers in addressing and resolving this barrier to optimal patient care. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Impact of a pharmacist-led warfarin self-management program on quality of life and anticoagulation control: a randomized trial.

PubMed

Verret, Lucie; Couturier, Justine; Rozon, Andréanne; Saudrais-Janecek, Sarah; St-Onge, Amélie; Nguyen, Angela; Basmadjian, Arsène; Tremblay, Simon; Brouillette, Denis; de Denus, Simon

2012-10-01

To evaluate the impact of a pharmacist-led warfarin patient self-management program on quality of life and anticoagulation control compared with management in a physician-led specialized anticoagulation clinic. Prospective, randomized, controlled, open-label trial. Tertiary care academic medical center. A total of 114 patients aged 18-75 years who were followed at a specialized anticoagulation clinic, had received warfarin for at least 6 months, and were expected to continue warfarin for a minimum of 4 months. All patients attended an educational session on anticoagulation provided by a pharmacist. Patients randomized to the self-management group (58 patients) also received practical training to use the CoaguChek XS device and a self-management dosing algorithm. Patients in the control group (56 patients) continued to undergo standard management at the anticoagulation clinic. Patients completed a validated quality-of-life questionnaire and the validated Oral Anticoagulation Knowledge test at the beginning and end of the study. The quality of anticoagulation control was evaluated by using the time spent in therapeutic range. After 4 months of follow-up, a significant improvement in the self-management group was observed compared with the control group in four of the five quality-of-life topics (p<0.05). Improvements in knowledge were observed in both groups after the training session and persisted after 4 months (p<0.05 for all). The time spent in the therapeutic range (80.0% in the self-management group vs 75% in the control group, p=0.79) and in the extended therapeutic range ([target international normalized ratio ± 0.3] 93.2% in the self-management group vs 91.1% in the control group, p=0.30) were similar between groups. A self-management warfarin program led by pharmacists resulted in significant improvement in the quality of life of patients receiving warfarin therapy as well as a reduction in the time required for anticoagulation monitoring, while

Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants.

PubMed

Cuker, Adam; Siegal, Deborah M; Crowther, Mark A; Garcia, David A

2014-09-16

Non-vitamin K oral anticoagulants (NOACs) do not require routine laboratory monitoring. However, laboratory measurement may be desirable in special situations and populations. This study's objective was to systematically review and summarize current evidence regarding laboratory measurement of the anticoagulant activity of dabigatran, rivaroxaban, and apixaban. We searched PubMed and Web of Science for studies that reported a relationship between drug levels of dabigatran, rivaroxaban, and apixaban and coagulation assay results. Study quality was evaluated using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2). We identified 17 eligible studies for dabigatran, 15 for rivaroxaban, and 4 for apixaban. For dabigatran, a normal thrombin time excludes clinically relevant drug concentrations. The activated partial thromboplastin time (APTT) and prothrombin time (PT) are less sensitive and may be normal at trough drug levels. The dilute thrombin time (R(2) = 0.92 to 0.99) and ecarin-based assays (R(2) = 0.92 to 1.00) show excellent linearity across on-therapy drug concentrations and may be used for drug quantification. For rivaroxaban and apixaban, anti-Xa activity is linear (R(2) = 0.89 to 1.00) over a wide range of drug levels and may be used for drug quantification. Undetectable anti-Xa activity likely excludes clinically relevant drug concentrations. The PT is less sensitive (especially for apixaban); a normal PT may not exclude clinically relevant levels. The APTT demonstrates insufficient sensitivity and linearity for quantification. Dabigatran, rivaroxaban, and apixaban exhibit variable effects on coagulation assays. Understanding these effects facilitates interpretation of test results in NOAC-treated patients. More information on the relationship between drug levels and clinical outcomes is needed. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Short-Term Anticoagulant Therapy and Thrombus Location Are Independent Risk Factors for Delayed Recanalization of Deep Vein Thrombosis

PubMed Central

Zhang, Chuanlin; Fu, Qining; Zhao, Yu; Mu, Shaoyu; Liu, Liping

2016-01-01

Background Prompt recanalization of the vein containing the thrombus is an important goal during the initial treatment of DVT, and risk factors for delayed recanalization in patients with deep vein thrombosis (DVT) in the lower extremities need to be determined. Material/Methods A total of 174 patients with DVT in lower extremities were recruited from June 2014 to March 2015 at our hospital. Duplex ultrasound scanning was conducted for all patients at 1 and 6 months after baseline evaluation. We divided the patients into recanalization and non-recanalization groups and analyzed risk factors for delayed recanalization. Results The univariate analysis revealed that an oral anticoagulant time of less than 3 months and venous thrombus location were risk factors for delayed recanalization (P<0.01). However, age, gender, hypertension, diabetes, pulmonary embolism, incidence factors, the use of catheter-directed thrombolytic (CDT) drugs, and inferior vena cava filter (IVCF) implantation had no influence on the incidence of delayed recanalization in patients with DVT (P>0.05). The multivariate analysis showed that patients with an anticoagulant time of less than 3 months had a lower incidence of recanalization than those with an anticoagulant time of more than 3 months (OR=2.358, P<0.05). The risk of delayed recanalization in patients with proximal DVT was 7 times higher than that in patients with distal DVT. Conclusions Duration of anticoagulant treatment of less than 3 months and venous thrombus location are independent risk factors for delayed recanalization of DVT in the lower extremities. PMID:26790571

Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry.

PubMed

Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph Gabriel

2015-01-01

Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. ISRCTN registry of clinical trials: ISRCTN43070564.

Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry

PubMed Central

Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M.; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph. Gabriel

2015-01-01

Background Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. Methods and Findings CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. Conclusions In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. Trial Registration ISRCTN registry of clinical trials: ISRCTN43070564. PMID:25915904

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study.

PubMed

Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Acciarresi, Monica; D'Amore, Cataldo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Mosconi, Maria Giulia; Bubba, Valentina; Silvestri, Ilenia; Lees, Kennedy R

2015-08-01

The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered

Variations in Anticoagulation Practices Following the Maze Procedure.

PubMed

Chung, Jennifer; Sami, Magdi; Albert, Carole; Varennes, Benoit De

2015-01-01

The current real-world anticoagulation practices following left atrial appendectomy in the context of the Maze procedure are unknown. This is a cohort study of all patients who underwent the Maze procedure with amputation of the left atrial appendage from June 2005 to November 2012. Data was prospectively collected at regular intervals with an interview and Holter monitoring. All patients received anticoagulation for 3 months. Those then kept on anticoagulation and those for whom anticoagulation was stopped were compared in terms of death, bleeding and incidence of stroke. In total, there were 113 patients, of whom 66 were treated with anticoagulation (Group A) and 47 were not (Group B). There were no significant baseline differences between the two groups, including the presence of atrial fibrillation (A:19.7%, B:10.6%, p=0.30), CHADS2 score (A:1.41±1.05, B:1.15±1.08, p=0.19), and left atrial size (A:48.3±7.1mm, B:47.6±7.8 mm, p=0.57). There were 275 patient-years of follow-up, with an average of 2.43 years per patient. Only two patients experienced strokes, both in Group A (p=0.27). Of the 5 bleeding events, 4 occurred in the first 3 months while on anticoagulation and the remaining event occurred in Group A at 3 years post-operatively (p=0.10). No standardized approach to anticoagulation after the Maze procedure is apparent in real-world practice in an urban Canadian setting. Patients who undergo the Maze procedure with amputation of the left atrial appendage are at a low risk of stroke, but the optimal anticoagulation strategy requires further investigation.

[Update on the control of patients on treatment with vitaminK antagonist oral anticoagulants in Primary Care].

PubMed

Fernández López, P; López Ramiro, M I; Merino de Haro, I; Cedeño Manzano, G; Díaz Siles, F J; Hermoso Sabio, A

In Spain, more than 80% of patients with atrial fibrillation (AF) receive oral anticoagulant therapy (OAT), and 72% of these patients are followed up in the Primary Care (PC) setting. Recent studies have shown that there is insufficient control of patients on OAT. The objective of the present study was to obtain more detailed information on the state of control of patients on treatment with vitaminK antagonist (VKA) oral anticoagulants (OAC), on the diseases for which the therapy was indicated and on concomitant diseases. This was a retrospective, cross-sectional, observational study with the participation of patients from a single health area included in an OAT programme throughout 2014. In patients on treatment with OAC, International Normalised Ratio (INR) control was considered insufficient when the percentage time in therapeutic range (TTR) was below 65% during an evaluation period of at least 6months. A total of 368 patients were included in the study, where the most frequent indication for oral anticoagulation was non-valvular AF. A total of 5,128 INR controls were performed, of which 2,359 (46%) were outside the therapeutic range, and 2,769 (54%) were within range. The risk of thromboembolism was very high in 91% of patients on treatment with VKA OAC. The indication for anticoagulation is correct in our population, assuming a low-intermediate risk of haemorrhage in the majority of patients. Measurement of the TTR using the Rosendaal method shows that the control of patients on treatment with VKA OAC is insufficient. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Anticoagulation for nonvalvular atrial fibrillation: effects of type of practice on physicians' self-reported behavior.

PubMed

Bush, D; Tayback, M

1998-02-01

This study examines whether social and economic factors affect physician practice and attitude with regard to warfarin anticoagulation in patients with nonvalvular atrial fibrillation. We identified physicians in Baltimore City, Baltimore County, and Prince George's County who (1) had written one or more prescriptions for a digitalis compound during the preceding year, and (2) were classified as general practitioners, family practice specialists, internists, or cardiologists. All 358 physicians fulfilling these criteria were surveyed by questionnaire. The overall response rate was 43%. Physicians who wrote 15% or more of their digitalis prescriptions for Medicaid patients said they used warfarin at significantly lower rates for patients with nonvalvular AF than other (66% versus 79%, P <0.01). The opposite pattern was seen with regard to aspirin. There were no significant differences in practice pattern between physicians located in urban vs. suburban counties. In our sample, self-reported anticoagulant practices for patients with nonvalvular AF were associated with the percentage of digitalis prescriptions written for Medicaid patients. In this metropolitan area, anticoagulant therapy was reportedly prescribed for approximately 75% of patients with nonvalvular atrial fibrillation.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines-Anticoagulation During Cardiopulmonary Bypass.

PubMed

Shore-Lesserson, Linda; Baker, Robert A; Ferraris, Victor A; Greilich, Philip E; Fitzgerald, David; Roman, Philip; Hammon, John W

2018-02-01

Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence. To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved

Efficacy of protocol-based pharmacotherapy management on anticoagulation with warfarin for patients with cardiovascular surgery.

PubMed

Katada, Y; Nakagawa, S; Minakata, K; Odaka, M; Taue, H; Sato, Y; Yonezawa, A; Kayano, Y; Yano, I; Nakatsu, T; Sakamoto, K; Uehara, K; Sakaguchi, H; Yamazaki, K; Minatoya, K; Sakata, R; Matsubara, K

2017-10-01

Anticoagulation therapy with warfarin requires periodic monitoring of prothrombin time-international normalized ratio (PT-INR) and adequate dose adjustments based on the data to minimize the risk of bleeding and thromboembolic events. In our hospital, we have developed protocol-based pharmaceutical care, which we called protocol-based pharmacotherapy management (PBPM), for warfarin therapy. The protocol requires pharmacists to manage timing of blood sampling for measuring PT-INR and warfarin dosage determination based on an algorithm. This study evaluated the efficacy of PBPM in warfarin therapy by comparing to conventional pharmaceutical care. From October 2013 to June 2015, a total of 134 hospitalized patients who underwent cardiovascular surgeries received post-operative warfarin therapy. The early series of patients received warfarin therapy as the conventional care (control group, n=77), whereas the latter received warfarin therapy based on the PBPM (PBPM group, n=68). These patients formed the cohort of the present study and were retrospectively analysed. The indications for warfarin included aortic valve replacement (n=56), mitral valve replacement (n=4), mitral valve plasty (n=22) and atrial fibrillation (n=29). There were no differences in patients' characteristics between both groups. The percentage time in therapeutic range in the first 10 days was significantly higher in the PBPM group (47.1%) than that in the control group (34.4%, P<.005). The average time to reach the steady state was significantly (P<.005) shorter in the PBPM group compared to the control group (7.3 vs 8.6 days). Warfarin therapy based on our novel PBPM was clinically safe and resulted in significantly better anticoagulation control compared to conventional care. © 2017 John Wiley & Sons Ltd.

WE-A-BRD-01: MR Imaging for Treatment Planning: What Every Physicist Should Know

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGee, K.

2015-06-15

Ever since its introduction as a diagnostic imaging modality over 30 years ago, the radiation therapy community has acknowledged the utility of MR imaging as a tool for not only improved visualization of the target volume but also for demarcation of adjacent organs at risk. However, the adaptation of MR imaging in radiation oncology has, until recently been slow due in large part to the inability to image radiation therapy patients in their treatment position. With the introduction of so-called wide bore high field MR scanners, multi element flexible receive only RF coils, high performance imaging gradients and a rangemore » of volumetric imaging sequences it is now possible to obtain both high resolution and high signal-to-noise ratio images of in-treatment radiation therapy patients within clinically feasible imaging times. As a Result, there is renewed interest in the use of MR imaging for radiation oncology treatment planning that is being translated into physical siting and integration of these systems into radiation oncology departments. As MR imaging expands into the radiation oncology domain there is a significant and unmet need for radiation therapy physicists to become educated regarding the strengths, limitations and technical challenges associated with MR imaging. The purpose of this presentation is to address this need by providing an educational overview of the techniques and challenges associated with MR imaging of patients for radiation therapy treatment planning. As such this presentation will: 1) describe the fundamental differences between imaging of patients for diagnostic and therapeutic purposes (i.e. radiation therapy planning), 2) describe most commonly used imaging sequences and contrasts for identification of disease for radiation planning, 3) identify the most common sources of image distortion and techniques to reduce their effect on spatial fidelity of the MR data, 4) describe the effects of motion and methods to quantify/correct it

Anticoagulation in pregnant women with mechanical heart valve prostheses

PubMed Central

Meschengieser, S; Fondevila, C; Santarelli, M; Lazzari, M

1999-01-01

OBJECTIVE—To evaluate the outcome of pregnancy in women with mechanical heart valve prostheses in relation to the anticoagulant treatment used in the first trimester and the incidence of thrombotic and bleeding complications.
METHODS—92 pregnancies in 59 women were followed between 1986 and 1997. In 31 pregnancies, oral anticoagulants were discontinued when pregnancy was diagnosed and subcutaneous heparin was started (12 500 U every 12 hours) adjusted to prolong the adjusted partial thromboplastin time to twice the control level. In the second trimester oral anticoagulants were resumed but changed to heparin again 15 days before the expected delivery date. In 61 pregnancies oral anticoagulants were continued during the first trimester. The same regimen of heparin was used for delivery.
RESULTS—Abortion or fetal losses were similar (p = 0.5717) in women exposed to oral anticoagulants in the first trimester (13/61; 25%) compared with those who received adjusted subcutaneous heparin (6/31; 19%). Embolic episodes were more common (p = 0.0029) in women who received heparin (4.92%) compared with those on oral anticoagulants (0.33%). Embolic episodes were cerebral and transient. No valve thromboses were observed. No malformations appeared in the 71 newborns, except for one case of hydrocephalus. There were no maternal deaths secondary to thrombotic complications. The only death was the result of major bleeding after the delivery of a premature stillborn.
CONCLUSIONS—Oral anticoagulants seem to be safer for the mother than adjusted subcutaneous heparin. Heparin does not offer a clear advantage over oral anticoagulation in the pregnancy outcome.


Keywords: pregnancy; oral anticoagulants; heparin; prosthetic valves PMID:10377303

Role of Pharmacogenomics in the Management of Traditional and Novel Oral Anticoagulants

PubMed Central

Cavallari, Larisa H.; Shin, Jaekyu; Perera, Minoli A.

2013-01-01

Warfarin is the most commonly prescribed oral anticoagulant. However, it remains a difficult drug to manage mostly because of its narrow therapeutic index and wide interpatient variability in anticoagulant effects. Over the past decade, there has been substantial progress in our understanding of genetic contributions to variable warfarin response, particularly with regard to warfarin dose requirements. The genes encoding for cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) are the major genetic determinants of warfarin pharmacokinetics and pharmacodynamics, respectively. Numerous studies have demonstrated significant contributions of these genes to warfarin dose requirements. The CYP2C9 gene has also been associated with bleeding risk with warfarin. The CYP4F2 gene influences vitamin K availability and makes minor contributions to warfarin dose requirements. Less is known about genes influencing warfarin response in African-American patients compared with other racial groups, but this is the focus of ongoing research. Several warfarin pharmacogenetic dosing algorithms and United States Food and Drug Administration–cleared genotyping tests are available for clinical use. Clinical trials are ongoing to determine the clinical utility and cost-effectiveness of genotype-guided warfarin dosing. Results from these trials will likely influence clinical uptake and third party payer reimbursement for genotype-guided warfarin therapy. There is still a lack of pharmacogenetic data for the newly approved oral anticoagulants, dabigatran and rivaroxaban, and with other oral anticoagulants in the research and development pipeline. These data, once known, could be of great importance as routine monitoring parameters for these agents are not available. PMID:22122181

Efficacy of aprotinin with various anticoagulant agents in cardiopulmonary bypass.

PubMed

Terrell, M R; Walenga, J M; Koza, M J; Pifarré, R

1996-08-01

Aprotinin has recently been approved for clinical use in cardiopulmonary bypass. Although unfractionated heparin has been the only anticoagulant widely used for cardiopulmonary bypass, disadvantages involving heparin have led to ongoing investigations of alternative anticoagulant agents. The objective of this study was to evaluate the efficacy of aprotinin in combination with other anticoagulant agents, specifically low molecular weight heparin and recombinant hirudin, using a dog model of cardiopulmonary bypass. The blood conservation resulting from the use of aprotinin was observed only with unfractionated heparin. Efficacy of anticoagulation as measured by protein deposits in the bypass circuit filter revealed an unexpected reduction in the quantity of deposits when aprotinin was used in combination with low molecular weight heparin. As alternative anticoagulant agents are sought, the potential benefits of aprotinin in the reduction of operative blood loss must be evaluated independently for each anticoagulant agent.

Postpartum wound and bleeding complications in women who received peripartum anticoagulation.

PubMed

Limmer, Jane S; Grotegut, Chad A; Thames, Elizabeth; Dotters-Katz, Sarah K; Brancazio, Leo R; James, Andra H

2013-07-01

The objective of this study was to compare wound and bleeding complications between women who received anticoagulation after cesarean delivery due to history of prior venous thromboembolic disease, arterial disease, or being a thrombophilia carrier with adverse pregnancy outcome, to women not receiving anticoagulation. Women in the Duke Thrombosis Center Registry who underwent cesarean delivery during 2003-2011 and received postpartum anticoagulation (anticoagulation group, n=77), were compared with a subset of women who delivered during the same time period, but did not receive anticoagulation (no anticoagulation group, n=77). The no anticoagulation group comprised women who were matched to the anticoagulation group by age, body mass index, type of cesarean (no labor vs. labor), and date of delivery. Bleeding and wound complications were compared between the two groups. A multivariable logistic regression model was constructed to determine if anticoagulation was an independent predictor of wound complication. Women who received anticoagulation during pregnancy had a greater incidence of wound complications compared to those who did not (30% vs. 8%, p<0.001). Using multivariable logistic regression, while controlling for race, diabetes, chorioamnionitis, and aspirin use, anticoagulation predicted the development of any wound complication (OR 5.8, 95% CI 2.2, 17.6), but there were no differences in the mean estimated blood loss at delivery (782 vs. 778 ml, p=0.91), change in postpartum hematocrit (5.4 vs. 5.2%, p=0.772), or percent of women receiving blood products (6.5 vs. 1.3%, p=0.209) between the two groups. Anticoagulation following cesarean delivery is associated with an increased risk of post-cesarean wound complications, but not other postpartum bleeding complications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention: a viewpoint.

PubMed

Gwyn, Jennifer C V; Thomas, Mark R; Kirchhof, Paulus

2017-07-01

Patients undergoing percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy to reduce the risk of subsequent myocardial infarction (MI) and stent thrombosis. Approximately 5-10% of patients undergoing PCI also have atrial fibrillation (AF). Patients with AF have an additional requirement for anticoagulation, as dual antiplatelet therapy alone is insufficient to adequately reduce the risk of stroke in patients with AF. However, it is now well established that combining anticoagulants with dual antiplatelet therapy also causes a significant increase in the risk of bleeding. Hence, there is great interest in discovering the optimal blend of antiplatelet therapy and oral anticoagulation in this situation, aiming to reduce the risk of stent thrombosis, recurrent MI, and stroke, while also minimizing the risk of bleeding. Recent studies have experimented with combining oral anticoagulation with a single antiplatelet agent, rather than combining oral anticoagulation with dual antiplatelet therapy. These studies show that this reduces the risk of bleeding but are underpowered to determine whether this still provides as much cardiovascular benefit. This review summarizes the currently available evidence on this topic and highlights the key questions that remain to be answered including ongoing clinical trials in the field. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Ultrasound therapy in iliopsoas hematoma.

PubMed

Kaya, Basak Bilir; Icagasioglu, Afitap

2017-01-01

Warfarin is a commonly used anticoagulant agent that can have life-threatening complications, such as severe bleeding, which then require cessation of the treatment. Due to the widespread use of this therapy in recent years, incidences of its hemorrhagic complications have also increased significantly. In hemodynamically stable patients, it is possible to adopt conservative treatment strategies, such as ultrasound (US) therapy as an alternative. US is a physical therapy modality widely used in musculoskeletal disorders, but there is little evidence about its effectiveness for hemorrhagic complications because of the limited number of studies on this subject at present. A 77-year-old male who had been under oral anticoagulant therapy for 6½ years presented at the clinic with complaints of severe pain and numbness in the anterolateral thigh. US evaluation revealed iliopsoas hematoma. US treatment, administered as a physical therapy modality, resulted in faster resorption of the hematoma than expected. The patient fully recovered from clinically observed pain, meralgia paresthetica, and reduced patellar reflex.

APOLLO I: Anticoagulation control in atrial fibrillation.

PubMed

Pinho-Costa, Luís; Moreira, Sónia; Azevedo, Cristiana; Azevedo, Pedro; Castro, Elisabete; Sousa, Hélder; Melo, Miguel

2015-05-01

Anticoagulation control as assessed by time in therapeutic range (TTR) correlates positively with the safety and efficacy of thromboprophylaxis in atrial fibrillation. We set out to assess TTR in our unit and to investigate determinants of better control. This was a case series study of atrial fibrillation patients anticoagulated with warfarin or acenocoumarol at the Family Health Unit of Fânzeres. Sociodemographic and clinical data were collected and TTR was calculated by the Rosendaal method, based on international normalized ratio tests performed in external laboratories in the preceding six months. SPSS 21.0 was used for the statistical analysis, with descriptive statistics, Spearman's correlation, and the Mann-Whitney U and Kruskal-Wallis tests. Of the 106 eligible patients, 70% participated in the study. Median TTR was 65.3% (P25=48.3%, P75=86.8%). We found a positive association between this variable and duration of atrial fibrillation (ρ=0.477, p<0.001, r(2)=0.116) and with duration of anticoagulation (ρ=0.5, p<0.001, r(2)=0.087). No association was found with age, gender, educational level or existence of a caregiver (p>0.05). Median TTR in our unit is similar to that in southern European countries and close to the good control threshold (70%) proposed by the European Society of Cardiology. The duration of atrial fibrillation and of anticoagulation explains only a small part of the measure's variability. Other determinants of anticoagulation control must be investigated in future studies and comparative studies should be carried out in family health units monitoring anticoagulation on the premises. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Determination of non-Vitamin K oral anticoagulant (NOAC) effects using a new-generation thrombelastography TEG 6s system.

PubMed

Bliden, Kevin P; Chaudhary, Rahul; Mohammed, Nafees; Muresan, Adina A; Lopez-Espina, Carlos G; Cohen, Eli; Raviv, Gabriel; Doubleday, Marc; Zaman, Fowzia; Mathew, Blessy; Tantry, Udaya S; Gurbel, Paul A

2017-05-01

Non vitamin K oral anticoagulants (NOACs) do not require regular monitoring but information about their pharmacodynamic effect may be importantin situations like trauma, stroke oremergent surgery. Currently, no standardized point-of-care test is available to evaluate the anticoagulant effects of NOACs. We evaluated the anticoagulant effect of NOACs with the next generation point-of-care TEG assay (TEG® 6S) based on a fully-automated thrombelastography system. We used two TEG® 6S assays, the DTI assay and Anti-Factor Xa (AFXa) assay, to detect anticoagulant effects and classify NOACs. Blood from healthy volunteers (n = 26) was used to obtain a baseline reference range. Data derived from patients on factor Xa inhibitors (FXi) (rivaroxaban and apixaban) (n = 39), and direct thrombin inhibitors (DTIs) (dabigatran) (n = 25) were compared against the reference range for detection of drug effect and drug classification. TEG®6s R-time highly correlated to each NOAC. Presence of NOACs caused elongation of R-time on the AFXa assay compared to the reference range (4.3 ± 1.7 vs. 1.3 ± 0.3 min. for FXi, p < 0.001 and 3.5 ± 1.2 vs. 1.3 ± 0.3 min. for DTI, p < 0.001). R-time on the DTI assay was elongated only in presence of a DTI (3.4 ± 1.0 vs. 1.5 ± 0.2 min, p < 0.001). The cutoff for detection of a DTI effect was an R time of 1.9 min and for anti-Xa effect was 1.95 min. For detection of NOAC therapy, there was ≥92% sensitivity and ≥95% specificity. The automated TEG®6s NOAC assay may be an effective tool to identify an anticoagulant effect from NOAC therapy and facilitate care of patients with bleeding or at risk of bleeding in the event of needing emergency surgery.

Flavocoxid, an anti-inflammatory agent of botanical origin, does not affect coagulation or interact with anticoagulation therapies.

PubMed

Pillai, Lakshmi; Levy, Robert M; Yimam, Mesfin; Zhao, Yuan; Jia, Qi; Burnett, Bruce P

2010-06-01

Flavocoxid, a botanical, anti-inflammatory agent, nonspecifically inhibits the peroxidase activity of cyclooxygenase (COX-1 and COX-2) enzymes and 5-lipooxygenase (5-LOX). Due to the concomitant use of aspirin or warfarin in many osteoarthritis (OA) patients with increased cardiovascular risk, we felt it necessary to assess the anticoagulation properties of flavocoxid. Three different studies were used: 1) a mouse model to assess effects on bleeding times when combined with aspirin; 2) the effect on platelet function as evaluated by platelet aggregation and bleed times in healthy human subjects; and 3) the effect on international normalized ratio in previously warfarinized patients with OA. Flavocoxid at a human equivalent dose (HED) of 569 mg (within the standard human dosing range of 500 mg) produced no significant increases in bleeding time in mice. There was also no inhibition or synergistic increase in bleed times when flavocoxid was combined with aspirin (370 mg HED). Flavocoxid did not significantly inhibit thromboxane production or platelet aggregation, and did not increase bleeding times in healthy volunteers. Finally, flavocoxid did not inhibit or potentiate the anticoagulant effect of warfarin. These results suggest that flavocoxid does not affect the primary or extrinsic pathways of secondary hemostasis and, by not inhibiting the anticoagulation effects of aspirin, may have utility in cardiovascular patients with OA.

[Prevention and treatment of venous thromboembolism: the place of new oral anticoagulants].

PubMed

Reis, Abílio

2012-04-01

Venous thromboembolism (VTE) is still an important problem of Public Health, due to its impact in terms of morbidity, mortality, resource allocation and associated costs. In the prevention and treatment of VTE, pharmacological therapy is well defined and efficacious but has some inconveniences that leave space for improvement. Several new oral anticoagulants are being developed and tested for the prevention and treatment of VTE. The better studied are the selective Factor Xa inhibitors apixaban, rivaroxaban and edoxaban, and the thrombin antagonist dabigatran. They all are orally administrated, don't have important interactions with food or other drugs, have a convenient fixed-dose regimen and a predictable action, and dispense routine monitoring of their anticoagulant effect. The major part of them has phase III studies concluded and published. Some of them are already approved by de European Medicines Agency (EMA) and the Food and Drug Administration (FDA) and recommended by the international guidelines. Rivaroxaban is approved by the EMA for the treatment of deep venous thrombosis (DVT) and for the prevention of recurrences of DVT and pulmonary embolism. In this article the available evidences are reviewed, the place of the new oral anticoagulants is discussed and future perspectives regarding the prevention and treatment of VTE are outlined. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Patient Education on Oral Anticoagulation.

PubMed

Hawes, Emily M

2018-04-20

Given the potential harm associated with anticoagulant use, patient education is often provided as a standard of care and emphasized across healthcare settings. Effective anticoagulation education involves face-to-face interaction with a trained professional who ensures that the patient understands the risks involved, the precautions that should be taken, and the need for regular monitoring. The teaching should be tailored to each patient, accompanied with written resources and utilize the teach-back method. It can be incorporated in a variety of pharmacy practice settings, including in ambulatory care clinics, hospitals, and community pharmacies.

k-space sampling optimization for ultrashort TE imaging of cortical bone: Applications in radiation therapy planning and MR-based PET attenuation correction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Lingzhi, E-mail: hlingzhi@gmail.com, E-mail: raymond.muzic@case.edu; Traughber, Melanie; Su, Kuan-Hao

Purpose: The ultrashort echo-time (UTE) sequence is a promising MR pulse sequence for imaging cortical bone which is otherwise difficult to image using conventional MR sequences and also poses strong attenuation for photons in radiation therapy and PET imaging. The authors report here a systematic characterization of cortical bone signal decay and a scanning time optimization strategy for the UTE sequence through k-space undersampling, which can result in up to a 75% reduction in acquisition time. Using the undersampled UTE imaging sequence, the authors also attempted to quantitatively investigate the MR properties of cortical bone in healthy volunteers, thus demonstratingmore » the feasibility of using such a technique for generating bone-enhanced images which can be used for radiation therapy planning and attenuation correction with PET/MR. Methods: An angularly undersampled, radially encoded UTE sequence was used for scanning the brains of healthy volunteers. Quantitative MR characterization of tissue properties, including water fraction and R2{sup ∗} = 1/T2{sup ∗}, was performed by analyzing the UTE images acquired at multiple echo times. The impact of different sampling rates was evaluated through systematic comparison of the MR image quality, bone-enhanced image quality, image noise, water fraction, and R2{sup ∗} of cortical bone. Results: A reduced angular sampling rate of the UTE trajectory achieves acquisition durations in proportion to the sampling rate and in as short as 25% of the time required for full sampling using a standard Cartesian acquisition, while preserving unique MR contrast within the skull at the cost of a minimal increase in noise level. The R2{sup ∗} of human skull was measured as 0.2–0.3 ms{sup −1} depending on the specific region, which is more than ten times greater than the R2{sup ∗} of soft tissue. The water fraction in human skull was measured to be 60%–80%, which is significantly less than the >90% water fraction

Transcatheter Arterial Embolization of Concurrent Spontaneous Hematomas of the Rectus Sheath and Psoas Muscle in Patients Undergoing Anticoagulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basile, Antonio; Medina, Jose Garcia; Mundo, Elena

We report a case of concurrent rectus sheath and psoas hematomas in a patient undergoing anticoagulant therapy, treated by transcatheter arterial embolization (TAE) of inferior epigastric and lumbar arteries. Computed tomography (CT) demonstrated signs of active bleeding in two hematomas of the anterior and posterior abdominal walls. Transfemoral arteriogram confirmed the extravasation of contrast from the right inferior epigastric artery (RIEA). Indirect signs of bleeding were also found in a right lumbar artery (RLA). We successfully performed TAE of the feeding arteries. There have been few reports in the literature of such spontaneous hemorrhages in patients undergoing anticoagulation, successfully treatedmore » by TAE.« less

Acute major gastrointestinal bleeding caused by hookworm infection in a patient on warfarin therapy: A case report.

PubMed

Meng, Yu; Lu, FangGen; Shi, Lin; Cheng, MeiChu; Zhang, Jie

2018-03-01

The use of anticoagulants is a contributor to gastrointestinal (GI) bleeding. Most bleeding patients on anticoagulant therapy such as warfarin commonly have basic lesions existing in their GI mucosa. We report a case of major GI bleeding following the use of anticoagulants in a patient with hookworm infection. The patient was diagnosed with nephrotic syndrome with pulmonary embolism. He was treated with anticoagulants and suffered from acute major GI bleeding during the treatment. Capsule endoscopy revealed many hookworms in the lumen of jejunum where fresh blood was seen coming from the mucosa. The patient was successfully rescued and cured with albendazole. Latent hookworm infection can be a cause of massive small-bowel hemorrhage in patients on anticoagulant therapy and anthelmintic treatment is the key to stop bleeding.

Effect of sodium citrate based anticoagulants on the growth activity of malaria parasites.

PubMed

Liu, Zhong-xiang; Wang, Xian-feng; Li, Shu-mei; Li, Xun; Xue, Cai-fang; Miao, Jun

2004-12-01

To study the effect of anticoagulants based on sodium citrate on the growth activity of malaria parasites. The parasites were treated with 3 anticoagulants (ACD, CD and SC), respectively, and the parasitemia was determined to measure the effect of the anticoagulants on the growth of the parasites. Unsynchronized Plasmodium falciparum was treated with the anticoagulants at different concentrations for 3 h at 37 degrees C. Treated erythrocytes were mixed with normal parasites or treated parasites with normal erythrocytes, which was followed by parasitemia determination of the two cultures to determine the cell target of the anticoagulants. Stage-synchronized parasites (ring, trophozoite and schizont) were treated as above to investigate the stage target. P. berghei was also treated with anticoagulants and inoculated in mice to detect the effect of anticoagulants on the animal malaria parasite by counting the parasitemia. All 3 anticoagulants inhibited falciparum parasite growth and ACD had the strongest potency. The treatments of the erythrocyte and the parasite with anticoagulants respectively showed that the anticoagulants targeted the parasites rather than normal erythrocytes. Stage-synchronized parasite treatment suggested anticoagulants primarily inhibited schizonts. The effect of anticoagulants on P. berghei was similar to that on P. falciparum. ACD showed the most significant inhibitive effect on the growth of malaria parasites and SC was the best anticoagulant based on sodium citrate for malarial experiments.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines-Anticoagulation During Cardiopulmonary Bypass.

PubMed

Shore-Lesserson, Linda; Baker, Robert A; Ferraris, Victor A; Greilich, Philip E; Fitzgerald, David; Roman, Philip; Hammon, John W

2018-02-01

Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence. To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved

[Interest of MR perfusion and MR spectroscopy for the diagnostic of atypical cerebral toxoplasmosis].

PubMed

Barcelo, C; Catalaa, I; Loubes-Lacroix, F; Cognard, C; Bonneville, F

2010-03-01

We report an atypical case of cerebral toxoplasmosis (CT) in a 70-year-old woman with a history of breast cancer. Contrast-enhanced computed tomography revealed a single ring-enhancing lesion in the pons with perifocal oedema and mass effect. Toxoplasma encephalitis was suggested by means of diffusion weighted imaging, MR perfusion and MR spectroscopy, leading to the discovery of HIV infection. The patient was put on antitoxoplasma therapy. Subsequent clinical and radiological improvements confirmed the diagnosis. (c) 2009 Elsevier Masson SAS. All rights reserved.

Multinational development of a questionnaire assessing patient satisfaction with anticoagulant treatment: the 'Perception of Anticoagulant Treatment Questionnaire' (PACT-Q©)

PubMed Central

Prins, Martin H; Marrel, Alexia; Carita, Paulo; Anderson, David; Bousser, Marie-Germaine; Crijns, Harry; Consoli, Silla; Arnould, Benoit

2009-01-01

Background The side effects and burden of anticoagulant treatments may contribute to poor compliance and consequently to treatment failure. A specific questionnaire is necessary to assess patients' needs and their perceptions of anticoagulant treatment. Methods A conceptual model of expectation and satisfaction with anticoagulant treatment was designed by an advisory board and used to guide patient (n = 31) and clinician (n = 17) interviews in French, US English and Dutch. Patients had either atrial fibrillation (AF), deep venous thrombosis (DVT), or pulmonary embolism (PE). Following interviews, three PACT-Q language versions were developed simultaneously and further pilot-tested by 19 patients. Linguistic validations were performed for additional language versions. Results Initial concepts were developed to cover three areas of interest: 'Treatment', 'Disease and Complications' and 'Information about disease and anticoagulant treatment'. After clinician and patient interviews, concepts were further refined into four domains and 17 concepts; test versions of the PACT-Q were then created simultaneously in three languages, each containing 27 items grouped into four domains: "Treatment Expectations" (7 items), "Convenience" (11 items), "Burden of Disease and Treatment" (2 items) and "Anticoagulant Treatment Satisfaction" (7 items). No item was deleted or added after pilot testing as patients found the PACT-Q easy to understand and appropriate in length in all languages. The PACT-Q was divided into two parts: the first part to measure the expectations and the second to measure the convenience, burden and treatment satisfaction, for evaluation prior to and after anticoagulant treatment, respectively. Eleven additional language versions were linguistically validated. Conclusion The PACT-Q has been rigorously developed and linguistically validated. It is available in 14 languages for use with thromboembolic patients, including AF, PE and DVT patients. Its validation and

Fundamentals of quantitative dynamic contrast-enhanced MR imaging.

PubMed

Paldino, Michael J; Barboriak, Daniel P

2009-05-01

Quantitative analysis of dynamic contrast-enhanced MR imaging (DCE-MR imaging) has the power to provide information regarding physiologic characteristics of the microvasculature and is, therefore, of great potential value to the practice of oncology. In particular, these techniques could have a significant impact on the development of novel anticancer therapies as a promising biomarker of drug activity. Standardization of DCE-MR imaging acquisition and analysis to provide more reproducible measures of tumor vessel physiology is of crucial importance to realize this potential. The purpose of this article is to review the pathophysiologic basis and technical aspects of DCE-MR imaging techniques.

Benefit, risk and cost of new oral anticoagulants and warfarin in atrial fibrillation; A multicriteria decision analysis.

PubMed

Mendoza-Sanchez, Jose; Silva, Federico; Rangel, Lady; Jaramillo, Linda; Mendoza, Leidy; Garzon, Jenny; Quiroga, Andrea

2018-01-01

Warfarin and new oral anticoagulants are effective in reducing stroke in atrial fibrillation; however, the benefits and risks rates in clinical trials show heterogeneity for each anticoagulant, and is unknown the cost influence on a model considering most of the treatment consequences. We designed a benefit-risk and cost assessment of oral anticoagulants. We followed the roadmap proposed by IMI-PROTECT and the considerations of emerged good practice to perform Multi-Criteria Decision Analysis (MCDA). The roadmap defines the following steps: (1) planning, (2) evidence gathering and data preparation, (3) analyses, (4) explorations, and (5) conclusions. We defined two reference points (0-100) to allocate numerical values for scores and weights, and used an analogue numeric scale to assess physicians' preferences. As benefits of the anticoagulant therapy, we included reductions in stroke and all-cause mortality; intracranial haemorrhage, gastrointestinal haemorrhage, minor bleeding and myocardial infarction were considered risks. We also made an estimation of the annual drug cost per person. The scores were: Apixaban 33, Dabigatrán 25, warfarin 18 and Rivaroxaban 14 this score reveals the most preferred up to the less preferred option, considering the benefit-risk ratio and drug costs altogether. The relative model weights were: 51.1% for risks, 40.4% for benefits and 8.5% for cost. The sensitivity analysis confirms the model robustness. From this analysis, apixaban should be considered as the preferred anticoagulant option -due to a better benefit-risk balance and a minor cost influence- followed by dabigatran, warfarin and rivaroxaban.

Simultaneous radiofrequency (RF) heating and magnetic resonance (MR) thermal mapping using an intravascular MR imaging/RF heating system.

PubMed

Qiu, Bensheng; El-Sharkawy, Abdel-Monem; Paliwal, Vaishali; Karmarkar, Parag; Gao, Fabao; Atalar, Ergin; Yang, Xiaoming

2005-07-01

Previous studies have confirmed the possibility of using an intravascular MR imaging guidewire (MRIG) as a heating source to enhance vascular gene transfection/expression. This motivated us to develop a new intravascular system that can perform MR imaging, radiofrequncy (RF) heating, and MR temperature monitoring simultaneously in an MR scanner. To validate this concept, a series of mathematical simulations of RF power loss along a 0.032-inch MRIG and RF energy spatial distribution were performed to determine the optimum RF heating frequency. Then, an RF generator/amplifier and a filter box were built. The possibility for simultaneous RF heating and MR thermal mapping of the system was confirmed in vitro using a phantom, and the obtained thermal mapping profile was compared with the simulated RF power distribution. Subsequently, the feasibility of simultaneous RF heating and temperature monitoring was successfully validated in vivo in the aorta of living rabbits. This MR imaging/RF heating system offers a potential tool for intravascular MR-mediated, RF-enhanced vascular gene therapy.

In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

NASA Astrophysics Data System (ADS)

Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong

2011-05-01

Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.

Differences in lupus anticoagulant final conclusion through clotting time or Rosner index for mixing test interpretation.

PubMed

Depreter, Barbara; Devreese, Katrien M J

2016-09-01

Lupus anticoagulant (LAC) testing includes a screening, mixing and confirmation step. Although recently published guidelines on LAC testing are a useful step towards standardization, a lack of consensus remains whether to express mixing tests in clotting time (CT) or index of circulating anticoagulant (ICA). The influence of anticoagulant therapy, e.g. vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) on both methods of interpretation remains to be investigated. The objective of this study was to contribute to a simplification and standardization of the LAC three-step interpretation on the level of the mixing test. Samples from 148 consecutive patients with LAC request and prolonged screening step, and 77 samples from patients non-suspicious for LAC treated with VKA (n=37) or DOAC (n=30) were retrospectively evaluated. An activated partial thromboplastin time (aPTT) and dilute Russell's viper venom time (dRVVT) were used for routine LAC testing. The supplemental anticoagulant samples were tested with dRVVT only. We focused on the interpretation differences for mixing tests expressed as CT or ICA and compared the final LAC conclusion within each distinct group of concordant and discordant mixing test results. Mixing test interpretation by CT resulted in 10 (dRVVT) and 16 (aPTT) more LAC positive patients compared to interpretation with ICA. Isolated prolonged dRVVT screen mix ICA results were exclusively observed in samples from VKA-treated patients without suspicion for LAC. We recommend using CT in respect to the 99th percentile cut-off for interpretation of mixing steps in order to reach the highest sensitivity and specificity in LAC detection.

Cost effectiveness of novel oral anticoagulants for stroke prevention in atrial fibrillation depending on the quality of warfarin anticoagulation control.

PubMed

Janzic, Andrej; Kos, Mitja

2015-04-01

Vitamin K antagonists, such as warfarin, are standard treatments for stroke prophylaxis in patients with atrial fibrillation. Patient outcomes depend on quality of warfarin management, which includes regular monitoring and dose adjustments. Recently, novel oral anticoagulants (NOACs) that do not require regular monitoring offer an alternative to warfarin. The aim of this study was to evaluate whether cost effectiveness of NOACs for stroke prevention in atrial fibrillation depends on the quality of warfarin control. We developed a Markov decision model to simulate warfarin treatment outcomes in relation to the quality of anticoagulation control, expressed as percentage of time in the therapeutic range (TTR). Standard treatment with adjusted-dose warfarin and improved anticoagulation control by genotype-guided dosing were compared with dabigatran, rivaroxaban, apixaban and edoxaban. The analysis was performed from the Slovenian healthcare payer perspective using 2014 costs. In the base case, the incremental cost-effectiveness ratio for apixaban, dabigatran and edoxaban was below the threshold of €25,000 per quality-adjusted life-years compared with adjusted-dose warfarin with a TTR of 60%. The probability that warfarin was a cost-effective option was around 1%. This percentage rises as the quality of anticoagulation control improves. At a TTR of 70%, warfarin was the preferred treatment in half the iterations. The cost effectiveness of NOACs for stroke prevention in patients with nonvalvular atrial fibrillation who are at increased risk for stroke is highly sensitive to warfarin anticoagulation control. NOACs are more likely to be cost-effective options in settings with poor warfarin management than in settings with better anticoagulation control, where they may not represent good value for money.

Interactive MR image guidance for neurosurgical and minimally invasive procedures

NASA Astrophysics Data System (ADS)

Wong, Terence Z.; Schwartz, Richard B.; Pergolizzi, Richard S., Jr.; Black, Peter M.; Kacher, Daniel F.; Morrison, Paul R.; Jolesz, Ferenc A.

1999-05-01

Advantages of MR imaging for guidance of minimally invasive procedures include exceptional soft tissue contrast, intrinsic multiplanar imaging capability, and absence of exposure to ionizing radiation. Specialized imaging sequences are available and under development which can further enhance diagnosis and therapy. Flow-sensitive imaging techniques can be used to identify vascular structures. Temperature-sensitive imaging is possible which can provide interactive feedback prior to, during, and following the delivery of thermal energy. Functional MR imaging and dynamic contrast-enhanced MRI sequences can provide additional information for guidance in neurosurgical applications. Functional MR allows mapping of eloquent areas in the brain, so that these areas may be avoided during therapy. Dynamic contrast enhancement techniques can be useful for distinguishing active tumor from tumor necrosis caused by previous radiation therapy. An open-configuration 0.5T MRI system (GE Signa SP) developed at Brigham and Women's Hospital in collaboration with General Electric Medical Systems is described. Interactive navigation systems have been integrated into the MRI system. The imaging system is sited in an operating room environment, and used for image guided neurosurgical procedures (biopsies and tumor excision), as well as minimally invasive thermal therapies. Examples of MR imaging guidance, navigational techniques, and clinical applications are presented.

Setting priorities in the health care sector - the case of oral anticoagulants in nonvalvular atrial fibrillation in Denmark.

PubMed

Poulsen, Peter Bo; Johnsen, Søren Paaske; Hansen, Morten Lock; Brandes, Axel; Husted, Steen; Harboe, Louise; Dybro, Lars

2017-01-01

Resources devoted to health care are limited, therefore setting priorities is required. It differs between countries whether decision-making concerning health care technologies focus on broad economic perspectives or whether focus is narrow on single budgets ("silo mentality"). The cost perspective as one part of the full health economic analysis is important for decision-making. With the case of oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF), the aim is to discuss the implication of the use of different cost perspectives for decision-making and priority setting. In a cost analysis, the annual average total costs of five oral anticoagulants (warfarin and non-vitamin K oral anticoagulants [NOACs; dabigatran, rivaroxaban, apixaban, and edoxaban]) used in daily clinical practice in Denmark for the prevention of stroke in NVAF patients are analyzed. This is done in pairwise comparisons between warfarin and each NOAC based on five potential cost perspectives, from a "drug cost only" perspective up to a "societal" perspective. All comparisons of warfarin and NOACs show that the cost perspective based on all relevant costs, ie, total costs perspective, is essential for the choice of therapy. Focusing on the reimbursement costs of the drugs only, warfarin is the least costly option. However, with the aim of therapy to prevent strokes and limit bleedings, including the economic impact of this, all NOACs, except rivaroxaban, result in slightly lower health care costs compared with warfarin. The same picture was found applying the societal perspective. Many broad cost-effectiveness analyses of NOACs exist. However, in countries with budget focus in decision-making this information does not apply. The present study's case of oral anticoagulants has shown that decision-making should be based on health care or societal cost perspectives for optimal use of limited resources. Otherwise, the risk is that suboptimal decisions will be likely.

Pheochromocytoma diagnosed after anticoagulation for atrial fibrillation ablation procedure: a giant in disguise.

PubMed

Galvão Braga, Carlos; Ribeiro, Sílvia; Martins, Juliana; Arantes, Carina; Ramos, Vítor; Primo, João; Magalhães, Sónia; Correia, Adelino

2014-04-01

Pheochromocytoma is a rare catecholamine-producing tumor, discovered incidentally in 50% of cases. We present the case of a 44-year-old male with a history of paroxysmal palpitations. Baseline ECG, transthoracic echocardiogram and ECG stress test showed no relevant alterations. Paroxysmal atrial fibrillation was detected on 24-hour Holter ECG. After antiarrhythmic therapy, the patient remained symptomatic, and was accordingly referred for electrophysiological study and atrial fibrillation ablation. Anticoagulation was initiated before the procedure. After ablation and still anticoagulated, he complained of hematospermia. The abdominal and pelvic imaging study showed a 10-cm left adrenal mass, predominantly cystic, compatible with pheochromocytoma, which was confirmed after biochemical tests (increased urine metanephrines and plasma catecholamines). Metaiodobenzylguanidine scintigraphy scanning confirmed localized disease in the adrenal gland, excluding other uptake foci. Following appropriate preoperative management, surgical resection of the giant mass was performed successfully and without complications. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol

PubMed Central

Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

2016-01-01

Introduction Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12–15% of patients with SSc and accounts for 30–40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. Methods and analysis This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethics and dissemination Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. Trial registration number ACTRN12614000418673, Pre-results. PMID:27932335

Optical sensing of anticoagulation status: Towards point-of-care coagulation testing

PubMed Central

Tripathi, Markandey M.; Hajjarian, Zeinab; Van Cott, Elizabeth M.; Nadkarni, Seemantini K.

2017-01-01

Anticoagulant overdose is associated with major bleeding complications. Rapid coagulation sensing may ensure safe and accurate anticoagulant dosing and reduce bleeding risk. Here, we report the novel use of Laser Speckle Rheology (LSR) for measuring anticoagulation and haemodilution status in whole blood. In the LSR approach, blood from 12 patients and 4 swine was placed in disposable cartridges and time-varying intensity fluctuations of laser speckle patterns were measured to quantify the viscoelastic modulus during clotting. Coagulation parameters, mainly clotting time, clot progression rate (α-angle) and maximum clot stiffness (MA) were derived from the clot viscoelasticity trace and compared with standard Thromboelastography (TEG). To demonstrate the capability for anticoagulation sensing in patients, blood samples from 12 patients treated with warfarin anticoagulant were analyzed. LSR clotting time correlated with prothrombin and activated partial thromboplastin time (r = 0.57–0.77, p<0.04) and all LSR parameters demonstrated good correlation with TEG (r = 0.61–0.87, p<0.04). To further evaluate the dose-dependent sensitivity of LSR parameters, swine blood was spiked with varying concentrations of heparin, argatroban and rivaroxaban or serially diluted with saline. We observed that anticoagulant treatments prolonged LSR clotting time in a dose-dependent manner that correlated closely with TEG (r = 0.99, p<0.01). LSR angle was unaltered by anticoagulation whereas TEG angle presented dose-dependent diminution likely linked to the mechanical manipulation of the clot. In both LSR and TEG, MA was largely unaffected by anticoagulation, and LSR presented a higher sensitivity to increased haemodilution in comparison to TEG (p<0.01). Our results establish that LSR rapidly and accurately measures the response of various anticoagulants, opening the opportunity for routine anticoagulation monitoring at the point-of-care or for patient self-testing. PMID:28771571

Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance.

PubMed

Martin, Karlyn A; Lee, Craig R; Farrell, Timothy M; Moll, Stephan

2017-05-01

Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited, and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of currently available data, it appears most prudent to use warfarin with international normalized ratio monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Mild brain injury and anticoagulants: Less is enough.

PubMed

Campiglio, Laura; Bianchi, Francesca; Cattalini, Claudio; Belvedere, Daniela; Rosci, Chiara Emilia; Casellato, Chiara Livia; Secchi, Manuela; Saetti, Maria Cristina; Baratelli, Elena; Innocenti, Alessandro; Cova, Ilaria; Gambini, Chiara; Romano, Luca; Oggioni, Gaia; Pagani, Rossella; Gardinali, Marco; Priori, Alberto

2017-08-01

Despite the higher theoretical risk of traumatic intracranial hemorrhage (ICH) in anticoagulated patients with mild head injury, the value of sequential head CT scans to identify bleeding remains controversial. This study evaluated the utility of 2 sequential CT scans at a 48-hour interval (CT1 and CT2) in patients with mild head trauma (Glasgow Coma Scale 13-15) taking oral anticoagulants. We retrospectively evaluated the clinical records of all patients on chronic anticoagulation treatment admitted to the emergency department for mild head injury. A total of 344 patients were included, and 337 (97.9%) had a negative CT1. CT2 was performed on 284 of the 337 patients with a negative CT1 and was positive in 4 patients (1.4%), but none of the patients developed concomitant neurologic worsening or required neurosurgery. Systematic routine use of a second CT scan in mild head trauma in patients taking anticoagulants is expensive and clinically unnecessary.

[Drug compliance of patients on anticoagulant treatment].

PubMed

Gadó, Klára; Kocsis, Eszter; Zelkó, Romána; Hankó, Balázs; Kovácsné Balogh, Judit; Forczig, Mónika; Domján, Gyula

2015-08-09

Despite several therapeutic possibilities the morbidity and mortality of thromboembolic disorders remain high. Improving drug compliance - i. e. keeping up the doctor's prescriptions - may be an effective tool to reach better results. To improve patients' compliance, the risk factors of non-compliance should be recognized. Among these patients' fear of adverse effects of drugs, their lack of knowledge about their illness and medication, forgetfulness, and other social, economic factors may be the most important. Furthermore, adherence may be worsened when the patient feels that the decision has been made over his/her head. Sustained medical adherence is important because anticoagulation may be a life-long treatment. The new oral anticoagulants make the matter of compliance to be current. These new type of drugs do not need regular laboratory monitoring and, therefore, compliance cannot be strictly followed. There are several studies concerning drug compliance to anticoagulant medications. Improvement of adherence is based on regular patient education after reviewing the factors of non-compliance, which needs teamwork with important roles of doctors, pharmacists, dietetics and nurses. Careful and accurate work of the participants of primary care might be complemented by the activity of anticoagulant clinics.

Magnesium flux during continuous venovenous haemodiafiltration with heparin and citrate anticoagulation.

PubMed

Brain, Matthew; Anderson, Mike; Parkes, Scott; Fowler, Peter

2012-12-01

To describe magnesium flux and serum concentrations in ICU patients receiving continuous venovenous haemodiafiltration (CVVHDF). Samples were collected from 22 CVVHDF circuits using citrate anticoagulation solutions (Prismocitrate 10/2 and Prism0cal) and from 26 circuits using Hemosol B0 and heparin anticoagulation. CVVHDF prescription, magnesium supplementation and anticoagulation choice was by the treating intensivist. We analysed 334 sample sets consisting of arterial, prefilter and postfilter blood and effluent. Magnesium loss was calculated from an equation for conservation of mass, and arterial magnesium concentration was described by an equation for exponential decay. Using flow rates typical of adults receiving CVVHDF, we determined a median half-life for arterial magnesium concentration to decay to a new steady state of 4.73 hours (interquartile range [IQR], 3.73-7.32 hours). Median arterial magnesium concentration was 0.88mmol/L (IQR, 0.83-0.97mmol/L) in the heparin group and 0.79mmol/L (IQR, 0.69-0.91mmol/L) in the citrate group. Arterial magnesium concentrations fell below the reference range regularly in the citrate group and, when low, there was magnesium flux from dialysate to patient. Magnesium loss was greater in patients receiving citrate. Exponential decline in magnesium concentrations was sufficiently rapid that subtherapeutic serum magnesium concentrations may occur well before detection when once-daily sampling was used. Measurements should be interpreted with regard to timing of magnesium infusions. We suggest that continuous renal replacement therapy fluids with higher magnesium concentrations be introduced in the critical care setting.

Stratifying the risks of oral anticoagulation in patients with liver disease.

PubMed

Efird, Lydia M; Mishkin, Daniel S; Berlowitz, Dan R; Ash, Arlene S; Hylek, Elaine M; Ozonoff, Al; Reisman, Joel I; Zhao, Shibei; Jasuja, Guneet K; Rose, Adam J

2014-05-01

Chronic liver disease presents a relative contraindication to warfarin therapy, but some patients with liver disease nevertheless require long-term anticoagulation. The goal is to identify which patients with liver disease might safely receive warfarin. Among 102 134 patients who received warfarin from the Veterans Affairs from 2007 to 2008, International Classification of Diseases-Ninth Revision codes identified 1763 patients with chronic liver disease. Specific diagnoses and laboratory values (albumin, aspartate aminotransferase, alanine aminotransferase, creatinine, and cholesterol) were examined to identify risk of adverse outcomes, while controlling for available bleeding risk factors. Outcomes included percent time in therapeutic range, a measure of anticoagulation control, and major hemorrhagic events, by International Classification of Diseases-Ninth Revision codes. Patients with liver disease had lower mean time in therapeutic range (53.5%) when compared with patients without (61.7%; P<0.001) and more hemorrhages (hazard ratio, 2.02; P<0.001). Among patients with liver disease, serum albumin and creatinine levels were the strongest predictors of both outcomes. We created a 4-point score system: patients received 1 point each for albumin (2.5-3.49 g/dL) or creatinine (1.01-1.99 mg/dL), and 2 points each for albumin (<2.5 g/dL) or creatinine (≥2 mg/dL). This score predicted both anticoagulation control and hemorrhage. When compared with patients without liver disease, those with a score of zero had modestly lower time in therapeutic range (56.7%) and no increase in hemorrhages (hazard ratio, 1.16; P=0.59), whereas those with the worst score (4) had poor control (29.4%) and high hazard of hemorrhage (hazard ratio, 8.53; P<0.001). Patients with liver disease receiving warfarin have poorer anticoagulation control and more hemorrhages. A simple 4-point scoring system using albumin and creatinine identifies those at risk for poor outcomes. © 2014 American

The prevalence of oral anticoagulation in patients with atrial fibrillation in Portugal: Systematic review and meta-analysis of observational studies.

PubMed

Caldeira, Daniel; Barra, Márcio; David, Cláudio; Costa, João; Ferreira, Joaquim J; Pinto, Fausto J

2014-09-01

Oral anticoagulation (OAC) is an effective treatment in the prevention of thromboembolic events in patients with atrial fibrillation (AF). The aim of this review was to estimate the prevalence of OAC therapy in patients with AF in Portugal. MEDLINE, the Index of Portuguese Medical Journals and SIBUL (the Bibliographic Catalog of the Integrated Library System of the University of Lisbon) were searched for Portuguese observational studies reporting the proportion of anticoagulated patients with AF. The pooled estimated prevalence of anticoagulated patients and respective 95% confidence interval (CI) were determined by means of a meta-analysis. Seven studies were included for analysis, of which four were conducted in a hospital environment and three in the general community. These studies enrolled a total of 891 patients with AF. The pooled estimated prevalence of anticoagulated patients was 40% (95% CI: 32-48%). The prevalence of OAC in Portuguese AF patients is low. There is a need to promote change in OAC prescribing habits for AF patients in Portugal, in accordance with international guidelines. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Therapeutic strategies after coronary stenting in chronically anticoagulated patients: the MUSICA study.

PubMed

Sambola, A; Ferreira-González, I; Angel, J; Alfonso, F; Maristany, J; Rodríguez, O; Bueno, H; López-Minguez, J R; Zueco, J; Fernández-Avilés, F; San Román, A; Prendergast, B; Mainar, V; García-Dorado, D; Tornos, P

2009-09-01

To identify the therapeutic regimens used at discharge in patients receiving oral anticoagulant therapy (OAT) who undergo stenting percutaneous coronary intervention and stent implantation (PCI-S), and to assess the safety and efficacy associated with different therapeutic regimens according to thromboembolic risk. A prospective multicentre registry. In hospital, after discharge and follow-up by telephone call. 405 patients (328 male/77 female; mean (SD) age 71 (9) years) receiving OAT who underwent PCI-S between November 2003 and June 2006 from nine catheterisation laboratories of tertiary care teaching hospitals in Spain and one in the United Kingdom were included. Three therapeutic regimens were identified at discharge: triple therapy (TT) -- that is, any anticoagulant (AC) plus double antiplatelet therapy (DAT; 278 patients (68.6%); AC and a single antiplatelet (AC+AT; 46 (11.4%)) and DAT only (81 (20%)). At 6 months, patients receiving TT showed the greatest rate of bleeding events. No patients receiving DAT at low thromboembolic risk presented a bleeding event (14.8% receiving TT, 11.8% receiving AC+AT and 0% receiving DAT, p = 0.033) or cardiovascular event (6.7% receiving TT, 0% receiving AC+AT and 0% receiving DAT, p = 0.126). The combination of AC+AT showed the worst rate of adverse events in the whole cohort, especially in patients at moderate-high thromboembolic risk. In patients receiving OAT, TT was the most commonly used regimen after PCI-S. DAT was associated with the lowest rate of bleeding events and a similar efficacy to TT in patients at low thromboembolic risk. TT should probably be restricted to patients at moderate-high thromboembolic risk.

Underuse of Anticoagulation in Older Patients with Atrial Fibrillation and CHADS2 Score ≥ 2: Are We Doing Better Since the Marketing of Direct Oral Anticoagulants?

PubMed

Henrard, Séverine; Vandenabeele, Caroline; Marien, Sophie; Boland, Benoit; Dalleur, Olivia

2017-11-01

Our objectives were to (1) describe the evolution of the underuse of anticoagulants in older people with atrial fibrillation (AF) and a CHADS 2 score ≥ 2 since direct oral anticoagulants (DOACs) were introduced to the market and (2) describe factors associated with this underuse. We conducted a retrospective cross-sectional study including geriatric patients admitted during the pre-DOAC (2008-2011) and post-DOAC (2013-2015) periods in an academic hospital in Belgium. Five inclusion criteria were met: age ≥ 75 years, diagnosis of AF, indication for anticoagulation (CHADS 2 score ≥ 2), risk of functional decline (Identification of Seniors At Risk [ISAR] score ≥ 2), and comprehensive geriatric assessment. The use of anticoagulants and antiplatelets at home before admission was recorded. Risks of stroke and bleeding were calculated using CHADS 2 and HEMORR 2 HAGES scores, respectively. Three different logistic regression models were performed to describe the evolution of and factors associated with the underuse of anticoagulants after DOAC marketing. Anticoagulant underuse, present in 209 of 614 (34%) geriatric patients with AF, was lower in patients with a history of stroke (28.5%) or congestive heart failure (26.9%) but higher in those receiving antiplatelets (56.2%) and in older individuals. Anticoagulant underuse decreased significantly from the pre-DOAC (37.3%) to the post-DOAC (29.7%) era, as shown by two analyses using propensity scores. In older patients with AF, anticoagulant underuse was mainly associated with antiplatelet use. Anticoagulant underuse and antiplatelet use have both decreased since DOAC marketing. Underuse of anticoagulants was still a concern for three in ten geriatric patients with AF at high risk of stroke (CHADS 2 score ≥ 2).

Anticoagulant Preferences and Concerns among Venous Thromboembolism Patients.

PubMed

Lutsey, Pamela L; Horvath, Keith J; Fullam, Lisa; Moll, Stephan; Rooney, Mary R; Cushman, Mary; Zakai, Neil A

2018-03-01

 Warfarin and direct oral anticoagulants (DOACs) are used for the initial treatment and secondary prevention of venous thromboembolism (VTE), and have similar efficacy. Patient concerns and preferences are important considerations when selecting an anticoagulant, yet these are not well studied.  VTE patients ( n  = 519) were surveyed from online sources (clotconnect.org, stoptheclot.org and National Blood Clot Alliance Facebook followers [ n  = 495]) and a haematology clinic in Vermont ( n  = 24).  Patients were 83% females and on average (±standard deviation [SD]) 45.7 ± 13.1 years; 65% self-reported warfarin as their initial VTE treatment and 35% a DOAC. Proportions reporting being extremely concerned about the following outcomes were as follows: recurrent VTE 33%, major bleeding 21%, moderate bleeding 16% and all-cause death 29%. When asked about oral anticoagulant characteristics, patients strongly preferred anticoagulants that are reversible (53%), and for which blood drug levels can be monitored (30%). Lower proportions agreed with statements that regular blood testing is inconvenient (18%), that they are comfortable using the newest drug versus an established drug (15%) and that it is difficult to change their diet to accommodate their anticoagulant (17%). In multivariable-adjusted models, patients tended to have had as their initial treatment, and to currently be taking, the oral anticoagulant option they personally preferred.  Patients held the greatest concern for recurrent VTE and mortality, regardless of which treatment they were prescribed. Potential weaknesses of warfarin (e.g., dietary restrictions, regular monitoring) were generally not considered onerous, while warfarin's advantages (e.g., ability to monitor) were viewed favourably. Schattauer GmbH Stuttgart.

SU-G-JeP2-04: Comparison Between Fricke-Type 3D Radiochromic Dosimeters for Real-Time Dose Distribution Measurements in MR-Guided Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, H; Alqathami, M; Wang, J

Purpose: To assess MR signal contrast for different ferrous ion compounds used in Fricke-type gel dosimeters for real-time dose measurements for MR-guided radiation therapy applications. Methods: Fricke-type gel dosimeters were prepared in 4% w/w gelatin prior to irradiation in an integrated 1.5 T MRI and 7 MV linear accelerator system (MR-Linac). 4 different ferrous ion (Fe2?) compounds (referred to as A, B, C, and D) were investigated for this study. Dosimeter D consisted of ferrous ammonium sulfate (FAS), which is conventionally used for Fricke dosimeters. Approximately half of each cylindrical dosimeter (45 mm diameter, 80 mm length) was irradiated tomore » ∼17 Gy. MR imaging during irradiation was performed with the MR-Linac using a balanced-FFE sequence of TR/TE = 5/2.4 ms. An approximate uncertainty of 5% in our dose delivery was anticipated since the MR-Linac had not yet been fully commissioned. Results: The signal intensities (SI) increased between the un-irradiated and irradiated regions by approximately 8.6%, 4.4%, 3.2%, and 4.3% after delivery of ∼2.8 Gy for dosimeters A, B, C, and D, respectively. After delivery of ∼17 Gy, the SI had increased by 24.4%, 21.0%, 3.1%, and 22.2% compared to the un-irradiated regions. The increase in SI with respect to dose was linear for dosimeters A, B, and D with slopes of 0.0164, 0.0251, and 0.0236 Gy{sup −1} (R{sup 2} = 0.92, 0.97, and 0.96), respectively. Visually, dosimeter A had the greatest optical contrast from yellow to purple in the irradiated region. Conclusion: This study demonstrated the feasibility of using Fricke-type dosimeters for real-time dose measurements with the greatest optical and MR contrast for dosimeter A. We also demonstrated the need to investigate Fe{sup 2+} compounds beyond the conventionally utilized FAS compound in order to improve the MR signal contrast in 3D dosimeters used for MR-guided radiation therapy. This material is based upon work supported by the National Science

Percutaneous Occlusion of the Left Atrial Appendage with the Watchman Device in an Active Duty Sailor with Atrial Fibrillation and Recurrent Thromboembolism Despite Appropriate Use of Oral Anticoagulation.

PubMed

Cox, Justin M; Choi, Anthony J; Oakley, Luke S; Francisco, Gregory M; Nayak, Keshav R

2018-05-23

Atrial fibrillation is the most common significant cardiac arrhythmia and is associated with a five-fold increased risk of stroke from thromboembolism. Over 94% of these emboli arise from the left atrial appendage. Systemic embolic phenomena are rare, accounting for less than 1 out of 10 of all embolic events, but have a similar prevention strategy. Anticoagulation significantly reduces the risk of these events, and thus forms the cornerstone of therapy for most patients with atrial fibrillation. Left atrial appendage occlusion with the Watchman device is a recently approved alternative for stroke prevention in selected patients. We present a case of an active duty U.S. Navy sailor at low risk for thromboembolism who nonetheless suffered recurrent thromboembolic events despite appropriate anticoagulation, and thus underwent Watchman implantation. The therapy in this case will ideally provide a lifetime of protection from recurrent systemic embolization while allowing the patient to continue his active duty military career without restriction due to oral anticoagulation.

Point-of-Care Coagulation Tests Monitoring of Direct Oral Anticoagulants and Their Reversal Therapy: State of the Art.

PubMed

Iapichino, Giacomo E; Bianchi, Paolo; Ranucci, Marco; Baryshnikova, Ekaterina

2017-06-01

Direct oral anticoagulants (DOACs) exert similar anticoagulant effects to vitamin K antagonists and are increasingly used worldwide. Nevertheless, an evidence-based approach to patients receiving DOACs when any unplanned urgent surgery or bleeding (either spontaneous or traumatic) occurs is still missing. In this review, we investigate the role of point-of-care coagulation tests when other, more specific tests are not available. Indeed, thromboelastography and activated clotting time can detect dabigatran-induced coagulopathy, while their accuracy is limited for apixaban and rivaroxaban, mostly in cases of low drug plasma concentrations. These tests can also be used to guide the reversal of DOAC-induced coagulopathy providing a quick, before-and-after picture in case of therapeutic use of hemostatic compounds. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Quality control of oral anticoagulant therapy in Primary Care in Madrid City, Spain: CHRONOS-TAO study].

PubMed

Alonso Roca, Rafael; Figueroa Guerrero, Carmen Arlene; Mainar de Paz, Victoria; Arribas García, M Paz; Sánchez Perruca, Luis; Rodríguez Barrientos, Ricardo; Casado López, Mariano; Pedraza Flechas, Ana M

2015-09-07

To determine quality control of patients with oral anticoagulant treatment recruited in Primary Care (PC) using the Rosendaal method to estimate time in therapeutic range (TTR) and comparing it with fraction of international normalized ratio (INR) in range and cross-sectional analysis (last INR registred). A retrospective observational study based on electronic medical record in routine clinical practice. PC centers (262) in Madrid. We included all patients with acenocumarol treatment, with an INR therapeutic range established between 2 and 3. We excluded patients with valvular pathology and disrupted clinical follow up in PC (<3 INR determinations in the studied period, a period of>90 days or ≥ 3 periods of>60 days between 2 determinations). The final population was 49,312 patients. The variables considered were all INR values and their respective dates. TTR was calculated by the 3 methods above mentioned. We considered "therapeutic range" INR between 2-3 and "adjusted range" INR between 1.8-3.2. Optimal control for each patient was considered TTR>60%. By using Rosendaal method, TTR was 66.8% (81.7% adjusted), with a percentage of total INR in range was 58.8% (66.5% adjusted), and, with the cross-sectional analysis, it was 70.5% (76.8% adjusted). Mean TTR was 65% (standard deviation 20.3), and the percentage of patients with TTR>60% was 63.3% (88.1% adjusted). The quality control of patients with oral anticoagulants in PC in Madrid is acceptable, similar or higher to other studies and pivotal trials of new anticoagulants. Compared to the Rosendaal method, total fraction of INR underestimates quality control, and cross-sectional analysis slightly overestimates it. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Accuracy and precision of patient positioning for pelvic MR-only radiation therapy using digitally reconstructed radiographs

NASA Astrophysics Data System (ADS)

Kemppainen, R.; Vaara, T.; Joensuu, T.; Kiljunen, T.

2018-03-01

Background and Purpose. Magnetic resonance imaging (MRI) has in recent years emerged as an imaging modality to drive precise contouring of targets and organs at risk in external beam radiation therapy. Moreover, recent advances in MRI enable treatment of cancer without computed tomography (CT) simulation. A commercially available MR-only solution, MRCAT, offers a single-modality approach that provides density information for dose calculation and generation of positioning reference images. We evaluated the accuracy of patient positioning based on MRCAT digitally reconstructed radiographs (DRRs) by comparing to standard CT based workflow. Materials and Methods. Twenty consecutive prostate cancer patients being treated with external beam radiation therapy were included in the study. DRRs were generated for each patient based on the planning CT and MRCAT. The accuracy assessment was performed by manually registering the DRR images to planar kV setup images using bony landmarks. A Bayesian linear mixed effects model was used to separate systematic and random components (inter- and intra-observer variation) in the assessment. In addition, method agreement was assessed using a Bland-Altman analysis. Results. The systematic difference between MRCAT and CT based patient positioning, averaged over the study population, were found to be (mean [95% CI])  -0.49 [-0.85 to  -0.13] mm, 0.11 [-0.33 to  +0.57] mm and  -0.05 [-0.23 to  +0.36] mm in vertical, longitudinal and lateral directions, respectively. The increases in total random uncertainty were estimated to be below 0.5 mm for all directions, when using MR-only workflow instead of CT. Conclusions. The MRCAT pseudo-CT method provides clinically acceptable accuracy and precision for patient positioning for pelvic radiation therapy based on planar DRR images. Furthermore, due to the reduction of geometric uncertainty, compared to dual-modality workflow, the approach is likely to improve the total

Anticoagulation therapy dramatically improved severe sigmoiditis with findings resembling inflammatory bowel disease, which was caused by mesenteric venous thrombosis.

PubMed

Mikami, Yohei; Kanai, Takanori; Iwasaki, Eisuke; Naganuma, Makoto; Yamagishi, Yoshiyuki; Shimoda, Masayuki; Matsuoka, Katsuyoshi; Hisamatsu, Tadakazu; Iwao, Yasushi; Ogata, Haruhiko; Nakatsuka, Seishi; Mukai, Makio; Hibi, Toshifumi

2012-12-01

Mesenteric venous thrombosis is an insidious disease, with a high mortality rate typically attributed to the long delay in diagnosis. Rapid diagnosis and treatment are important. Here, we present a patient with idiopathic inferior mesenteric venous (IMV) thrombosis. A 65-year-old man presented with constant abdominal pain associated with fever and bloody diarrhea. He was diagnosed with severe ulcerative colitis and was treated with mesalazine and prednisolone. The prednisolone was tapered because of liver dysfunction, and he received total parenteral nutrition for a month. His abdominal pain and bloody diarrhea worsened, and he lost 5 kg of weight. He was then transferred to our institute. Computed tomography showed thickening of the left colon. Colonoscopy showed diffuse colitis with multiple ulcers, large edematous folds, congested mucosa, and stenosis of the sigmoid colon, with sparing of the rectum, raising the possibility of IMV thrombosis. Angiography confirmed IMV thrombosis. Anticoagulation therapy was initiated with intravenous heparin followed by oral warfarin. His abdominal pain and diarrhea resolved, and he was discharged from hospital. Six months later, he remained asymptomatic with normal colonoscopic findings.

Idarucizumab for Reversing Dabigatran-Induced Anticoagulation: A Systematic Review.

PubMed

Thibault, Nathan; Morrill, Amanda M; Willett, Kristine C

The approval of the oral direct thrombin inhibitor, dabigatran etexilate, gave patients an alternative to oral anticoagulation with warfarin. Like all anticoagulants, the primary adverse event (AE) associated with dabigatran is bleeding. Until the FDA approval of idarucizumab, there had been no reversal agent for dabigatran-induced anticoagulation in patients with life-threatening or uncontrollable bleeding, or those requiring emergent procedures. The primary purpose of this review is to summarize the safety and efficacy of idarucizumab, a monoclonal antibody fragment, and its use as a reversal agent for dabigatran. A literature search was conducted through MEDLINE (1946 to November week 1 2015) and Embase (1980-2015 week 46) using the search term idarucizumab. Clinicaltrials.gov was consulted for a comprehensive list of ongoing and completed studies. Additional studies were identified through bibliographical citations. Clinical trials in animals and humans published in English evaluating the safety and efficacy of idarucizumab for reversal of anticoagulant treatment with dabigatran were included for review. Idarucizumab has been shown to significantly reverse the anticoagulant effects of dabigatran in both healthy volunteers and patients requiring a reversal agent because of either overt bleeding or an emergency surgery or invasive procedure. The most common AEs were headache, nasopharyngitis, back pain, skin irritation, hypokalemia, delirium, constipation, pyrexia, and pneumonia. Deaths reported in idarucizumab studies were attributed to either the index event or a preexisting comorbidity. Most adverse effects were minor, but 21 serious AEs have been reported in the published data including thrombotic events. Given the increased use of direct oral anticoagulants, such as dabigatran, a need for specific reversal agents exists. Idarucizumab has been shown to be safe and effective in the reversal of dabigatran-induced anticoagulation in patients requiring emergent

[The study of anticoagulants selection in platelet-rich plasma preparation].

PubMed

Hua, Lei; Lai, Gui; Zhenjun, Liu; Guie, Ma

2015-07-01

To investigate the effect of the anticoagulants on PRP quality, so as to clarify the appropriate anticoagulant used in PRP production. The microstructure change of platelets collected via heparin, citrate, acid citrate dextrose (ACD) and citrate-theophylline-adenosine-dipyridamole ( CTAD) was observed by TEM following time course. The extent of spontaneous activation of platelets in four groups was detected by measuring sP-selectin in plasma. The TGF-β1 release amount of activated PRP of four groups was measured. CTAD is superior to other anticoagulants in maintaining the integrity of platelet structures for a long time and preventing platelet spontaneous activation. ACD slightly surpassed heparin and citrate in above two aspects. ACD-PRP and CTAD-PRP released significantly more TGF-β1 compared with heparin and citrate. The PRP quality and biological effects were strongly associated with the type of Anticoagulants. ACD and CTAD are optimal anticoagulants in PRP production for they can maintain platelet viability at a high level.

Conformal thermal therapy using planar ultrasound transducers and adaptive closed-loop MR temperature control: demonstration in gel phantoms and ex vivo tissues

NASA Astrophysics Data System (ADS)

Tang, K.; Choy, V.; Chopra, R.; Bronskill, M. J.

2007-05-01

MRI-guided transurethral ultrasound therapy offers a minimally invasive approach for the treatment of localized prostate cancer. Integrating a multi-element planar transducer with active MR temperature feedback can enable three-dimensional conformal thermal therapy of a target region within the prostate gland while sparing surrounding normal tissues. Continuous measurement of the temperature distribution in tissue enables dynamic compensation for unknown changes in blood flow and tissue properties during treatment. The main goal of this study was to evaluate the feasibility of using active temperature feedback on a clinical 1.5 T MR imager for conformal thermal therapy. MR thermometry was performed during heating in both gel phantoms and excised tissue with a transurethral heating applicator, and the rotation rate and power were varied based on the thermal measurements. The capability to produce a region of thermal damage that matched a target boundary was evaluated. The influence of a cooling gradient (to simulate cooling of the rectum or urethra) on the desired pattern of thermal damage was also investigated in gel phantoms. Results showed high correlation between the desired target boundary and the 55 °C isotherm generated during heating with an average distance error of 0.9 mm ± 0.4 mm (n = 6) in turkey breasts, 1.4 mm ± 0.6 mm (n = 4) in gel phantoms without rectal cooling and 1.4 mm ± 0.6 mm (n = 3) in gel phantoms with rectal cooling. The results were obtained using a temporal update rate of 5 s, a spatial resolution of 3 × 3 × 10 mm for the control point, and a temperature uncertainty of approximately 1 °C. The performance of the control algorithm under these conditions was comparable to that of simulations conducted previously by our group. Overall, the feasibility of generating targeted regions of thermal damage with a transurethral heating applicator and active MR temperature feedback has been demonstrated experimentally. This method of treatment

Acute management of bleeding in patients on novel oral anticoagulants.

PubMed

Siegal, Deborah M; Crowther, Mark A

2013-02-01

Novel oral anticoagulants that directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are currently available for prevention of venous thromboembolism (VTE) after orthopaedic surgery, treatment of acute VTE, and prevention of arterial thromboembolism in non-valvular atrial fibrillation. These agents offer advantages over VKAs, including rapid onset, shorter half-lives, fewer drug interactions, and lack of need for routine monitoring. However, there are no established agents to reverse their anticoagulant effect. We review the risk of bleeding with the novel oral anticoagulants and the limitations of conventional coagulation assays for measuring anticoagulant effect. We provide an approach to the management of patients with bleeding complications with evidence for various interventions for reversal, where available.

Hemostasis and Post-operative Care of Oral Surgical Wounds by Hemcon Dental Dressing in Patients on Oral Anticoagulant Therapy: A Split Mouth Randomized Controlled Clinical Trial.

PubMed

Kumar, K R Ashok; Kumar, Jambukeshwar; Sarvagna, Jagadesh; Gadde, Praveen; Chikkaboriah, Shwetha

2016-09-01

Hemostasis is a fundamental management issue post-operatively in minor oral surgical procedures. To ensure safety and therapeutic efficacy in patients, under oral anti coagulant therapy, is complicated by necessity for frequent determination of prothrombin time or international normalised ratio. The aim of the study was to determine whether early hemostasis achieved by using Hemcon Dental Dressing (HDD) will affect post-operative care and surgical healing outcome in minor oral surgical procedures. A total of 30 patients, aged 18 years to 90 years, except those allergic to seafood, who consented to participate, were enrolled into this study. Patients were required to have two or more surgical sites so that they would have both surgical and control sites. All patients taking Oral Anticoagulation Therapy (OAT) were included for treatment in the study without altering the anticoagulant regimens. Institutional Review Board approval was obtained for the same. The collected data was subjected to statistical analysis using unpaired t-test. All HDD surgically treated sites achieved hemostasis in 1.49 minutes and control wounds in 4.06 minutes (p < 0.001). Post-operative pain at HDD treated sites (1.87,1.27 on 1 st and 3 rd day respectively) was significantly lower than the control sites (4.0,1.87 on 1 st and 3 rd day respectively) p-value (0.001, 0.001 respectively). HDD treated oral surgery wounds achieved statistically significant improved healing both at 1 st and 3 rd post-operative days (p <0.0001). The HDD has been proven to be a clinically effective hemostatic dressing material that significantly shortens bleeding time following minor oral surgical procedures under local anaesthesia, including those patients taking OAT. Patients receiving the HDD had improved surgical wound healing as compared to controls.

Causes of Death in Patients with Venous Thromboembolism Anticoagulated with Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis.

PubMed

Gómez-Outes, Antonio; Terleira-Fernández, Ana Isabel; Lecumberri, Ramón; Suárez-Gea, Mª Luisa; Calvo-Rojas, Gonzalo; Vargas-Castrillón, Emilio

2018-06-01

Death is more frequent than nonfatal recurrent venous thromboembolism (VTE) and major bleeding after acute VTE. The analysis of the causes of death is fundamental to explore new strategies to reduce mortality rates in these patients. The authors performed a meta-analysis to analyze mortality and independently adjudicated causes of death in anticoagulated patients due to VTE, and to evaluate potential differences between different anticoagulant schemes. They searched MEDLINE and CENTRAL, from January 1, 2000, to January 31, 2017, and performed additional searches in Web sites of regulatory agencies, clinical trial registers, and conference proceedings. Two investigators independently selected studies and extracted the data. Study quality was assessed with the Cochrane Collaboration's tool for assessing the risk of bias in randomized studies. Seven prospective randomized trials in 29,844 patients (22,025 patient-year follow-up) were included, comparing dabigatran, rivaroxaban, apixaban, and edoxaban with the standard anticoagulant treatment of VTE. A total of 718 patients died during the follow-up (3.4% per year; 95% confidence interval [CI]: 2.3-4.8). The most frequent causes of death were cancer (42%), followed by VTE (20%), infections (13%), hemorrhage (6%), heart disease (4%), and stroke (2%). There were no differences in the overall survival and causes of death according to the anticoagulant type. Concomitant active cancer during the study was significantly associated with death (odds ratio: 15.2; 95% CI: 9.2-25.1). Cancer is the leading cause of death in contemporary VTE trials. Interventions beyond anticoagulation, particularly in patients with active cancer, are needed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians

PubMed Central

Peacock, W. Frank; Rafique, Zubaid; Singer, Adam J.

2016-01-01

Nonvalvular atrial fibrillation- (NVAF-) related stroke and venous thromboembolism (VTE) are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs)—dabigatran, rivaroxaban, apixaban, and edoxaban—have been developed for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed. PMID:27293895

Prevention of thromboembolic events in patients with atrial fibrillation - new anticoagulants.

PubMed

Campos, Alexandre Holthausen; Cirenza, Cláudio

2011-09-01

The authors present alternatives for the treatment of cardiac arrhythmias. Its detection is based on the use of different methods that record the cardiac electrical activity. The treatment involves intervening in the underlying disorder, antiarrhythmic drugs, stimulation and cardiac defibrillation devices, and, less often, surgery. The technological advances in the last two decades have provided greater efficiency in diagnoses and therapy. Atrial fibrilation patients will benefit from a new set of anticoagulant drugs tested in the past three years. The potential advantages include greater safety and efficacy, as well as convenience for not requiring frequent laboratory controls.

[Ultrasound dynamics lysis apex thrombus as an objective criterion of effectiveness of anticoagulation therapy in venous thrombosis].

PubMed

Kalinin, R E; Suchkov, I A; Pshennikov, A S; Agapov, A B

2016-01-01

To assess the effectiveness of anticoagulant therapy (ACT) for the treatment of patients with deep venous thrombosis (DVT) of the lower extremities. The study considered ultrasonic characteristics of lysis of the proximal part of thrombus: localization and nature of venous thrombosis, the length and diameter of the proximal floating part of the thrombus, and duration of the venous thrombosis. Depending on the ACT options patients were divided into 3 groups: Group 1 (18 patients) received rivaroxaban, group 2 (19 patients) received enoxaparin sodium with subsequent transition to warfarin, and 3 group (19 patietns) received enoxaparin sodium, followed by administration of rivaroxaban. Treatment with rivaroxaban was preferable over standard ACT with enoxaparin/warfarin with regards to the lysis of thrombus when duration of thrombosis did not exceed 10 days. In 10.5% of patients who received warfarin flotation of thrombi remained for 14 days; the length of the floating part of the thrombi did not exceed 3 cm. Such circumstances and inability to reach a therapeutic INR value required cava filter placement. Treatment with enoxaparin sodium followed by the administration of rivaroxaban was found to be the most efficient ACT regimen as there was no negative dynamics of ultrasound characteristics of lysis of thrombi at any duration of the disease.

Antithrombotic Therapy for VTE Disease

PubMed Central

Kearon, Clive; Comerota, Anthony J.; Prandoni, Paolo; Bounameaux, Henri; Goldhaber, Samuel Z.; Nelson, Michael E.; Wells, Philip S.; Gould, Michael K.; Dentali, Francesco; Crowther, Mark; Kahn, Susan R.

2012-01-01

Background: This article addresses the treatment of VTE disease. Methods: We generated strong (Grade 1) and weak (Grade 2) recommendations based on high-quality (Grade A), moderate-quality (Grade B), and low-quality (Grade C) evidence. Results: For acute DVT or pulmonary embolism (PE), we recommend initial parenteral anticoagulant therapy (Grade 1B) or anticoagulation with rivaroxaban. We suggest low-molecular-weight heparin (LMWH) or fondaparinux over IV unfractionated heparin (Grade 2C) or subcutaneous unfractionated heparin (Grade 2B). We suggest thrombolytic therapy for PE with hypotension (Grade 2C). For proximal DVT or PE, we recommend treatment of 3 months over shorter periods (Grade 1B). For a first proximal DVT or PE that is provoked by surgery or by a nonsurgical transient risk factor, we recommend 3 months of therapy (Grade 1B; Grade 2B if provoked by a nonsurgical risk factor and low or moderate bleeding risk); that is unprovoked, we suggest extended therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high (Grade 1B); and that is associated with active cancer, we recommend extended therapy (Grade 1B; Grade 2B if high bleeding risk) and suggest LMWH over vitamin K antagonists (Grade 2B). We suggest vitamin K antagonists or LMWH over dabigatran or rivaroxaban (Grade 2B). We suggest compression stockings to prevent the postthrombotic syndrome (Grade 2B). For extensive superficial vein thrombosis, we suggest prophylactic-dose fondaparinux or LMWH over no anticoagulation (Grade 2B), and suggest fondaparinux over LMWH (Grade 2C). Conclusion: Strong recommendations apply to most patients, whereas weak recommendations are sensitive to differences among patients, including their preferences. PMID:22315268

Cerebral Venous Congestion as Indication for Thrombolytic Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, Fong Y., E-mail: ftsai@uci.edu; Kostanian, Varoujan; Rivera, Monica

Purpose. To carry out a retrospective analysis of patients with acute dural sinus thrombosis, and the role of cerebral venous congestion in patient management. Methods. Twenty-five patients were identified with the clinical and imaging diagnosis of acute dural sinus thrombosis. The imaging diagnosis was by magnetic resonance (MR) and/or computed tomography (CT) venography. There was a female predominance with a female to male ratio of 1.5 to 1 (16 women, 9 men). The age range was from 19 to 64 years old with an average age of 37 years. The first 10 patients, who ranged in age from 21 tomore » 64 years old (average 37 years), received only anticoagulation therapy with heparin and warfarin for periods ranging from 5 days to 2 months. The remaining 15 patients ranged in age from 19 to 57 years old (average 38 years). They either underwent subsequent thrombectomy after a trial of anticoagulation therapy, or went straight to thrombectomy. These latter 15 patients had initial evidence of cerebral venous congestion, either clinically by severe or worsening symptoms despite anticoagulation therapy, or on initial or subsequent CT or MR imaging. In our experience, the cerebral venous congestion imaging findings included intracranial hemorrhage, a hematoma, or edema. The thrombolytic treatment technique consisted of the advancement of a 6 Fr guiding catheter to the jugular bulb or sigmoid sinus from a transfemoral approach. A microcatheter was then advanced to the proximal portion of the thrombus and then either tissue plasminogen activator (tPA) or urokinase was injected to prevent clot propagation. A balloon catheter was used to perform thrombectomy since the thrombolytic agents can be injected via the inner lumen with an inflated balloon. The inflated balloon helped to keep the venous flow from washing out the thrombolytic agent, thus facilitating the agent's effect. Results. The first 10 patients received only anticoagulation therapy with heparin and warfarin for

Andexanet alfa to reverse the anticoagulant activity of factor Xa inhibitors: a review of design, development and potential place in therapy.

PubMed

Sartori, Michelangelo; Cosmi, Benilde

2018-04-01

Direct oral anticoagulants are associated with rates of major bleeding which are not negligible, albeit lower than those associated with vitamin K antagonists. No specific reversal agent for factor Xa (FXa) direct inhibitors is currently available for clinical use. A modified activated human FXa decoy protein, andexanet alfa, is being developed that binds FXa direct inhibitors in their active site, thus reversing their anticoagulant effect. The purpose of this article is to review the design, development and clinical trials of andexanet alfa. Andexanet alfa was shown to reverse FXa inhibitors anticoagulant activity both in thrombosis animal models, healthy volunteers and patients with acute major bleeding. Andexanet alfa has been studied in double-blind, placebo-controlled phase II and III studies. A preliminary report of the phase III study showed that an effective hemostasis was obtained after andexanet alfa infusion in the majority of the patients with acute major bleeding associated with FXa inhibitors. Additional studies are ongoing and andexanet alfa is expected to be launched in the market in the near future.

Trial Protocol: A randomised controlled trial of extended anticoagulation treatment versus routine anticoagulation treatment for the prevention of recurrent VTE and post thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (The ExACT Study)

PubMed Central

2013-01-01

Background Venous thromboembolism comprising pulmonary embolism and deep vein thrombosis is a common condition with an incidence of approximately 1 per 1,000 per annum causing both mortality and serious morbidity. The principal aim of treatment of a venous thromboembolism with heparin and warfarin is to prevent extension or recurrence of clot. However, the recurrence rate following a deep vein thrombosis remains approximately 10% per annum following treatment cessation irrespective of the duration of anticoagulation therapy. Patients with raised D-dimer levels after discontinuing oral anticoagulation treatment have also been shown to be at high risk of recurrence. Post thrombotic syndrome is a complication of a deep vein thrombosis which can lead to chronic venous insufficiency and ulceration. It has a cumulative incidence after 2 years of around 25% and it has been suggested that extended oral anticoagulation should be investigated as a possible preventative measure. Methods/design Patients with a first idiopathic venous thromboembolism will be recruited through anticoagulation clinics and randomly allocated to either continuing or discontinuing warfarin treatment for a further 2 years and followed up on a six monthly basis. At each visit D-dimer levels will be measured using a Roche Cobas h 232 POC device. In addition a venous sample will be taken for laboratory D-dimer analysis at the end of the study. Patients will be examined for signs and symptoms of PTS using the Villalta scale and complete VEINES and EQ5D quality of life questionnaires. Discussion The primary aim of the study is to investigate whether extending oral anticoagulation treatment (prior to discontinuing treatment) beyond 3–6 months for patients with a first unprovoked proximal deep vein thrombosis or pulmonary embolism prevents recurrence. The study will also determine the role of extending anticoagulation for patients with elevated D-dimer levels prior to discontinuing treatment and

WE-G-17A-01: Improving Tracking Image Spatial Resolution for Onboard MR Image Guided Radiation Therapy Using the WHISKEE Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Y; Mutic, S; Du, D

Purpose: To evaluate the feasibility of using the weighted hybrid iterative spiral k-space encoded estimation (WHISKEE) technique to improve spatial resolution of tracking images for onboard MR image guided radiation therapy (MR-IGRT). Methods: MR tracking images of abdomen and pelvis had been acquired from healthy volunteers using the ViewRay onboard MRIGRT system (ViewRay Inc. Oakwood Village, OH) at a spatial resolution of 2.0mm*2.0mm*5.0mm. The tracking MR images were acquired using the TrueFISP sequence. The temporal resolution had to be traded off to 2 frames per second (FPS) to achieve the 2.0mm in-plane spatial resolution. All MR images were imported intomore » the MATLAB software. K-space data were synthesized through the Fourier Transform of the MR images. A mask was created to selected k-space points that corresponded to the under-sampled spiral k-space trajectory with an acceleration (or undersampling) factor of 3. The mask was applied to the fully sampled k-space data to synthesize the undersampled k-space data. The WHISKEE method was applied to the synthesized undersampled k-space data to reconstructed tracking MR images at 6 FPS. As a comparison, the undersampled k-space data were also reconstructed using the zero-padding technique. The reconstructed images were compared to the original image. The relatively reconstruction error was evaluated using the percentage of the norm of the differential image over the norm of the original image. Results: Compared to the zero-padding technique, the WHISKEE method was able to reconstruct MR images with better image quality. It significantly reduced the relative reconstruction error from 39.5% to 3.1% for the pelvis image and from 41.5% to 4.6% for the abdomen image at an acceleration factor of 3. Conclusion: We demonstrated that it was possible to use the WHISKEE method to expedite MR image acquisition for onboard MR-IGRT systems to achieve good spatial and temporal resolutions simultaneously. Y. Hu and O

A multinational investigation of time and traveling costs in attending anticoagulation clinics.

PubMed

Jowett, Sue; Bryan, Stirling; Mahé, Isabelle; Brieger, David; Carlsson, Jonas; Kartman, Bernt; Nevinson, Mark

2008-01-01

Anticoagulation is used in patients with atrial fibrillation to reduce the risk of ischemic stroke. The therapy requires regular monitoring and, frequently, dose adjustment. This study aimed to determine the time and traveling costs that patients incur to themselves and society in attending anticoagulation clinics. A subset of patients from 105 primary and secondary care clinics allocated to the warfarin arm of SPORTIF III (patients from Australia, France, Portugal, Spain, Sweden, and the UK) completed a questionnaire. Patients indicated the type of transport used for clinic visits, and estimated traveling expenses. Patients were also asked to estimate total traveling and clinic attendance time, and to confirm whether they were currently employed and whether they had to give up time from work to attend the clinic. Time cost of companions was also taken into consideration. Cost per visit was calculated (euro, 2003 prices). Questionnaires for a total of 381 patients were analyzed, with the majority of patients from Sweden (n = 130) and the UK (n = 101). Mean cost to patients varied widely between countries, ranging from euro6.9 (France) to euro20.5 (Portugal) per visit. For most countries, time costs (value of lost working and leisure time) were the main driver of costs. Mean time cost to society ranged from euro5.6 (France) to euro31.7 (Portugal) per visit. Patients incur considerable costs when visiting anticoagulation clinics, and these costs vary by country. The results suggest the importance of taking a broad economic perspective when considering the cost-effectiveness of warfarin.

Disadvantages of VKA and requirements for novel anticoagulants.

PubMed

Shameem, Raji; Ansell, Jack

2013-06-01

Vitamin K antagonists have been in wide use for over 70 years. Warfarin, the most commonly used vitamin K antagonist, has been shown to be highly effective in treating and preventing thrombosis. Despite this, warfarin has many disadvantages, which has led to the development of a new class of oral anticoagulants targeted to specific coagulation factors designated as target-specific oral anticoagulants (TSOAs). TSOAs include the thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban). This chapter reviews the disadvantages of warfarin and evaluates both the advantages and disadvantages of the new oral anticoagulants. © 2013 Elsevier Ltd. All rights reserved.

Doxorubicin loaded superparamagnetic PLGA-iron oxide multifunctional microbubbles for dual-mode US/MR imaging and therapy of metastasis in lymph nodes.

PubMed

Niu, Chengcheng; Wang, Zhigang; Lu, Guangming; Krupka, Tianyi M; Sun, Yang; You, Yufang; Song, Weixiang; Ran, Haitao; Li, Pan; Zheng, Yuanyi

2013-03-01

Current strategies for tumor-induced sentinel lymph node detection and metastasis therapy have limitations. In this work, we co-encapsulated iron oxide nanoparticles and chemotherapeutic drug into poly(lactic-co-glycolic acid) (PLGA) microbubbles to form multifunctional polymer microbubbles (MPMBs) for both tumor lymph node imaging and therapy. Fe(3)O(4) nanoparticles and doxorubicin (DOX) co-encapsulated PLGA microbubbles were prepared and filled with perfluorocarbon gas. Enhancement of ultrasound (US)/magnetic resonance (MR) imaging and US triggered drug delivery were evaluated both in vitro and in vivo. The MPMBs exhibited characters like narrow size distribution and smooth surface with a mean diameter of 868.0 ± 68.73 nm. In addition, varying the concentration of Fe(3)O(4) nanoparticles in the bubbles did not significantly influence the DOX encapsulation efficiency or drug loading efficiency. Our in vitro results demonstrated that these MPMBs could enhance both US and MR imaging which was further validated in vivo showing that these MPMBs enhanced tumor lymph nodes signals. The anti-tumor effect of MPMBs mediated chemotherapy was assessed in vivo using end markers like tumor proliferation index, micro blood vessel density and micro lymphatic vessel density, which were shown consistently the lowest after the MPMBs plus sonication treatment compared to controls. In line with these findings, the tumor cell apoptotic index was found the largest after the MPMBs plus sonication treatment. In conclusion, we have successfully developed a doxorubicin loaded superparamagnetic PLGA-Iron Oxide multifunctional theranostic agent for dual-mode US/MR Imaging of lymph node, and for low frequency US triggered therapy of metastasis in lymph nodes, which might provide a strategy for the imaging and chemotherapy of primary tumor and their metastases. Copyright © 2012 Elsevier Ltd. All rights reserved.

Novel anticoagulants for stroke prevention in patients with atrial fibrillation.

PubMed

Jalota, A; Scarabelli, T M; Saravolatz, L; Bakhsh, M U; Agrawal, P; Jalota, R; Chen-Scarabelli, C; Fuster, V; Halperin, J

2014-06-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia that can potentially result in stroke. Vitamin K antagonists (VKA) like warfarin were for many decades the only oral anticoagulants available for stroke prevention in patients with non-valvular atrial fibrillation (AF) at high risk of stroke. Recently, new oral anticoagulants (NOACS) have been introduced that act via direct inhibition of thrombin (dabigatran) or activated factor X (edoxaban, rivaroxaban and apixaban). Unlike VKAs, these anticoagulants do not require routine INR monitoring and posses favorable pharmacological properties. NOACs act rapidly, and have a stable and predictable dose-related anticoagulant effect with few clinically relevant drug-drug interactions. Phase III trials comparing these agents to warfarin for stroke prevention in patients with non-valvular AF demonstrated that they are at least as efficacious and safe as warfarin. Evolution of clinical guidelines to incorporate the new anticoagulants for stroke prevention in non-valvular AF may result in a reduction in the incidence of AF-related strokes. Safe and effective use of these new drugs in clinical practice requires understanding of their distinct pharmacological properties.

Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review.

PubMed

Warkentin, Theodore E; Pai, Menaka; Linkins, Lori-Ann

2017-08-31

Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, ON, Canada, since January 1, 2015 (when we completed our prospective study of rivaroxaban for HIT), using rivaroxaban for serologically confirmed HIT (4Ts score ≥4 points; positive platelet factor 4 [PF4]/heparin immunoassay, positive serotonin-release assay). We also performed a literature review of HIT treatment using DOACs (rivaroxaban, apixaban, dabigatran, edoxaban). We focused on patients who received DOAC therapy for acute HIT as either primary therapy (group A) or secondary therapy (group B; initial treatment using a non-DOAC/non-heparin anticoagulant with transition to a DOAC during HIT-associated thrombocytopenia). Our primary end point was occurrence of objectively documented thrombosis during DOAC therapy for acute HIT. We found that recovery without new, progressive, or recurrent thrombosis occurred in all 10 Hamilton patients with acute HIT treated with rivaroxaban. Data from the literature review plus these new data identified a thrombosis rate of 1 of 46 patients (2.2%; 95% CI, 0.4%-11.3%) in patients treated with rivaroxaban during acute HIT (group A, n = 25; group B, n = 21); major hemorrhage was seen in 0 of 46 patients. Similar outcomes in smaller numbers of patients were observed with apixaban (n = 12) and dabigatran (n = 11). DOACs offer simplified management of selected patients, as illustrated by a case of persisting (autoimmune) HIT (>2-month platelet recovery with inversely parallel waning of serum-induced heparin-independent serotonin release) with successful outpatient rivaroxaban management of HIT-associated thrombosis. Evidence supporting efficacy and safety of DOACs for acute HIT is increasing, with the most experience reported for rivaroxaban. © 2017 by The American Society of Hematology.

Evaluation of the anticoagulant potential of polysaccharide-rich fractions extracted from macroalgae.

PubMed

Adrien, Amandine; Dufour, Delphine; Baudouin, Stanislas; Maugard, Thierry; Bridiau, Nicolas

2017-09-01

The aim of this study was to evaluate the potential anticoagulant activity of sulphated polysaccharide-containing extracts of six french edible marine macroalgae. Aqueous extracts of brown (Himanthalia elongata, Laminaria digitata, Ascophyllum nodosum, Fucus vesiculosus), green (Ulva lactuca) and red (Chondrus crispus) macroalgae were prepared and their biochemical properties were determined, including major biomolecules, sulphate and ash contents. The anticoagulant activity of each extract was investigated using different scales from the specific antithrombin-dependent pathway (anti-Xa and anti-IIa) to the intrinsic and/or common (Activated Partial Thromboplastin Time, APTT), extrinsic (Prothrombin Time, PT) or common (Thrombin Time, TT) anticoagulant pathways, and compared with those of commercial anticoagulants, heparin and Lovenox®. Laminaria digitata, Fucus vesiculosus and Chondrus crispus extracts showed a significant APTT anticoagulant capacity, only 5-fold lower than that of Lovenox®, which is a pure low molecular weight heparin used as an anticoagulant agent to prevent pulmonary embolism in patients undergoing surgery.

Managing the therapeutic dilemma: patients with spontaneous intracerebral hemorrhage and urgent need for anticoagulation.

PubMed

Bertram, M; Bonsanto, M; Hacke, W; Schwab, S

2000-03-01

Physicians face a therapeutic dilemma in patients with acute hemorrhagic stroke requiring long-term, high-intensity anticoagulants because this treatment increases the risk of intracranial hemorrhage (ICH) 8- to 11-fold. We retrospectively studied 15 patients with ICH which occurred under anticoagulation with phenprocoumon, with an international norrmalized ratio (INR) of 2.5-6.5 on admission. Hemispheric, thalamic, cerebellar, intraventricular, or subarachnoid hemorrhage without aneurysm occurred. Absolute indications for anticoagulation were double, mitral, or aortic valve replacement, combined mitral valve failure with atrial fibrillation and atrial enlargement, internal carotid artery-jugular vein graft, frequently recurring deep vein thrombosis with risk of pulmonary embolism, and severe nontreatable ischemic heart disease. As soon as the diagnosis of ICH was established, INR normalization was attempted in all patients by administration of prothrombin complex, fresh frozen plasma, or vitamin K. After giving phenprocoumon antagonists (and neurosurgical therapy in four patients) heparin administration was started. Nine patients received full-dose intravenous and six low-dose subcutaneous heparin. The following observations were made: (a) All patients with effective, full-dose heparin treatment with a 1.5- to 2-fold elevation in partial thromboplastin time after normalization of the INR were discharged without complication. (b) Three of four of the patients with only incomplete correction of the INR (> 1.35) experienced relevant rebleeding within 3 days (all patients with an INR higher than 1.5), two of whom were on full-dose heparin. (c) Three of seven of the patients with normalized INR and without significant PTT elevation developed severe cerebral embolism. Although our data are based on a retrospective analysis, they support treatment with intravenous heparin (partial thromboplastin time 1.5-2 times baseline value) after normalization of the INR in patients

[Management of new oral anticoagulants in gastrointestinal bleeding and endoscopy].

PubMed

del Molino, Fátima; Gonzalez, Isabel; Saperas, Esteve

2015-10-01

New oral direct anticoagulants agents are alternatives to warfarin for long-term anticoagulation in a growing number of patients that require long-term anticoagulation for atrial fibrillation, deep venous thrombosis and pulmonary embolism. These new agents with predictable pharmacokinetic and pharmacodynamics profiles offer a favorable global safety profile, but increased gastrointestinal bleeding compared to the vitamin K antagonists. Many gastroenterologists are unfamiliar and may be wary of these newer drugs, since Clinical experience is limited and no specific antidote is available to reverse their anticoagulant effect. In this article the risk of these new agents and, how to manage these agents in both the presence of acute gastrointestinal bleeding and in patients undergoing endoscopic procedures is reviewed. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer - A real world experience.

PubMed

Phelps, Megan K; Wiczer, Tracy E; Erdeljac, H Paige; Van Deusen, Kelsey R; Porter, Kyle; Philips, Gary; Wang, Tzu-Fei

2018-01-01

Introduction Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited. Objectives The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis. Secondary objectives were to determine the rates of clinically relevant-non-major bleeding and all-cause mortality. Patients/methods This is a retrospective cohort study including adults with cancer-associated thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant between 2010 and 2016 at the Ohio State University. Medical records were reviewed for 6 months after initiation of anticoagulation or until the occurrence of recurrent cancer-associated thrombosis, major bleeding, cessation of anticoagulation of interest, or death, whichever occurred first. Results Four hundred and eighty patients were included (290 low-molecular-weight heparin and 190 direct oral anticoagulant). Patients treated with direct oral anticoagulant were found to carry "lower risk" features including cancer with lower VTE risk and lower rate of metastatic disease. After adjustment for baseline differences, there was no significant difference in the rate of recurrent cancer-associated thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant, p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct oral anticoagulant, p = 0.08). Conclusions Our study demonstrates that in a select population of cancer patients with VTE, direct oral anticoagulant use can be as effective and safe compared to the standard therapy with low-molecular-weight heparin.

The Reversal of Direct Oral Anticoagulants in Animal Models

PubMed Central

Honickel, Markus; Akman, Necib; Grottke, Oliver

2017-01-01

ABSTRACT Several direct oral anticoagulants (DOACs), including direct thrombin and factor Xa inhibitors, have been approved as alternatives to vitamin K antagonist anticoagulants. As with any anticoagulant, DOAC use carries a risk of bleeding. In patients with major bleeding or needing urgent surgery, reversal of DOAC anticoagulation may be required, presenting a clinical challenge. The optimal strategy for DOAC reversal is being refined, and may include use of hemostatic agents such as prothrombin complex concentrates (PCCs; a source of concentrated clotting factors), or DOAC-specific antidotes (which bind their target DOAC to abrogate its activity). Though promising, most specific antidotes are still in development. Preclinical animal research is the key to establishing the efficacy and safety of potential reversal agents. Here, we summarize published preclinical animal studies on reversal of DOAC anticoagulation. These studies (n = 26) were identified via a PubMed search, and used rodent, rabbit, pig, and non-human primate models. The larger of these animals have the advantages of similar blood volume/hemodynamics to humans, and can be used to model polytrauma. We find that in addition to varied species being used, there is variability in the models and assays used between studies; we suggest that blood loss (bleeding volume) is the most clinically relevant measure of DOAC anticoagulation-related bleeding and its reversal. The studies covered indicate that both PCCs and specific reversal agents have the potential to be used as part of a clinical strategy for DOAC reversal. For the future, we advocate the development and use of standardized, clinically, and pharmacologically relevant animal models to study novel DOAC reversal strategies. PMID:28471371

Predictors of self-reported adherence to direct oral anticoagulation in a population of elderly men and women with non-valvular atrial fibrillation.

PubMed

Rossi, Andrea P; Facchinetti, Roberto; Ferrari, Elena; Nori, Nicole; Sant, Selena; Masciocchi, Elena; Zoico, Elena; Fantin, Francesco; Mazzali, Gloria; Zamboni, Mauro

2018-05-14

There is a general lack of studies evaluating medication adherence with self-report scales for elderly patients in treatment with direct oral anticoagulants (DOACs). The aim of the study was to assess the degree of adherence to DOAC therapy in a population of elderly outpatients aged 65 years or older affected by non-valvular atrial fibrillation (NVAF), using the 4-item Morisky Medication Adherence Scale, and to identify potential factors, including the geriatric multidimensional evaluation, which can affect adherence in the study population. A total of 103 subjects, anticoagulated with DOACs for NVAF in primary or secondary prevention, were eligible; 76 showed adequate adhesion to anticoagulant therapy, while 27 showed inadequate adherence. Participants underwent biochemical assessment and Morisky Scale, Instrumental Activities of Daily Living, CHA2DS2-VASc, HAS-BLED, mental status and nutritional evaluations were performed. 2% of subjects assumed Dabigatran at low dose, while 7.8% at standard dose, 9.7% assumed low-dose of Rivaroxaban and 30.1% at standard dose, 6.8% assumed Apixaban at low dose and 39.7% at standard dose, and finally 1% assumed Edoxaban at low dose and 2.9% at standard dose. Most subjects took the DOACs without help (80.6%), while 16 subjects were helped by a family member (15.5%) and 4 were assisted by a caregiver (3.9%). Binary logistic regression considered inappropriate adherence as a dependent variable, while age, male sex, polypharmacotherapy, cognitive decay, caregiver help for therapy assumption, duration of DOAC therapy and double daily administration were considered as independent variables. The double daily administration was an independent factor, determining inappropriate adherence with an OR of 2.88 (p = 0.048, CI 1.003-8.286).

Design of anticoagulant surfaces based on cellulose nanocrystals.

PubMed

Ehmann, Heike M A; Mohan, Tamilselvan; Koshanskaya, Maria; Scheicher, Sylvia; Breitwieser, Doris; Ribitsch, Volker; Stana-Kleinschek, Karin; Spirk, Stefan

2014-11-07

The anticoagulant activity of surfaces decorated with cellulose nanocrystals (CNCs) prepared via sulfuric acid hydrolysis, is explored. Such surfaces bear a high amount of negatively charged sulfate groups, which mimic the naturally occurring anticoagulant heparin in terms of charge density. It is demonstrated that CNC decorated surfaces significantly enhance the coagulation times of blood plasma and whole blood as proven by QCM-D and simple clotting tests.

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol.

PubMed

Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

2016-12-08

Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12-15% of patients with SSc and accounts for 30-40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. ACTRN12614000418673, Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

3D-MR Spectroscopic Imaging at 3Tesla for Early Response Assessment of Glioblastoma Patients during External Beam Radiation Therapy

PubMed Central

Muruganandham, Manickam; Clerkin, Patrick P; Smith, Brian J; Anderson, Carryn M; Morris, Ann; Capizzano, Aristides A; Magnotta, Vincent; McGuire, Sarah M; Smith, Mark C; Bayouth, John E; Buatti, John M

2014-01-01

Purpose To evaluate the utility of 3D-MR proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium enhanced MR images at simulation and at boost treatment planning after 17-20 fractions of radiotherapy. All patients received standard radiotherapy with temozolomide and follow-up with every two month MR scans. Progression free survival was defined using MacDonald criteria. MRSI images obtained at initial simulation were analyzed for choline / N-acetylaspartate ratios (Cho/NAA) on a voxel by voxel basis with abnormal activity defined as Cho/NAA ≥ 2. These images were compared on anatomically matched MRSI data collected after 3 weeks of radiotherapy. Changes in Cho/NAA between pre-therapy and 3rd week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results After 8.6 months (median follow-up), 50% of patients had progressed based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (p< 0.01). Patients with an increase in mean or median Cho/NAA values at the 3rd week RT scan had a significantly greater chance of early progression (p <0.01). An increased Cho/NAA at the 3rd week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval 1.10-6.71, p= 0.03). Most patients received the prescription dose of RT to the Cho/NAA ≥ 2 volume, which was where recurrence most often occurred. Conclusion Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested. PMID:24986746

High prevalence of iatrogenic hyperthyroidism in elderly patients with atrial fibrillation in an anticoagulation clinic.

PubMed

Krishnan, Sandeep Kumar; Dohrmann, Mary L; Brietzke, Stephen A; Fleming, David A; Flaker, Greg C

2011-01-01

In elderly patients with established atrial fibrillation (AF) who are receiving thyroid replacement, regular testing for thyroid function is often not performed, placing the patient at risk for iatrogenic hyperthyroidism. Of 215 patients followed in an anticoagulation clinic, 41 were receiving thyroid replacement and 15 of these were found to have hyperthyroidism. Eight had documented AF coincident with abnormal thyroid function. In addition, only 22 patients on thyroid replacement had an annual TSH. In conclusion, iatrogenic hyperthyroidism may frequently be missed in AF patients because of inadequate monitoring of serum TSH. Thyroid replacement is common in elderly patients with AF followed in an anticoagulation clinic. Laboratory evidence of hyperthyroidism occurred in 37%, usually in patients with higher doses of thyroid replacement, and often associated with AF. The frequency of iatrogenic hyperthyroidism may be underestimated in patients with AF since many patients who receive thyroid replacement therapy are not monitored regularly with serum TSH.

Rivaroxaban as an oral anticoagulant for stroke prevention in atrial fibrillation

PubMed Central

Turpie, Alexander GG

2014-01-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the developed world and is associated with a fivefold increase in the risk of stroke, accounting for up to 15% of strokes in the general population. The European Society of Cardiology now recommends direct oral anticoagulants, such as rivaroxaban, apixaban, and dabigatran, in preference to vitamin K antagonist therapy for the prevention of stroke in patients with A F. This review focuses on the direct Factor Xa inhibitor rivaroxaban, summarizing the properties that make rivaroxaban appropriate for anticoagulant therapy in this indication (including its predictable pharmacokinetic and pharmacodynamic profile and once-daily dosing regimen) and describing data from the Phase III ROCKET AF trial, which showed once-daily rivaroxaban to be noninferior to warfarin for the prevention of stroke in patients with nonvalvular AF. In this trial, similar rates of major and nonmajor clinically relevant bleeding were observed; however, when compared with warfarin, rivaroxaban was associated with clinically significant reductions in intracranial and fatal bleeding. On the basis of these results, rivaroxaban was approved in both the United States and the European Union for the prevention of stroke and systemic embolism in patients with nonvalvular AF. Subanalyses of ROCKET AF data showed rivaroxaban to have consistent efficacy and safety across a wide range of patients, and studies to confirm these results in real-world settings are underway. This review also describes practical considerations for treatment with rivaroxaban in clinical practice (including dose reductions in specific high-risk patients, eg, those with renal impairment), recommendations for the transition from vitamin K antagonists to rivaroxaban, the management of bleeding events, and the measurement of rivaroxaban exposure. PMID:24711702

Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding.

PubMed

Parks, Anna L; Fang, Margaret C

2017-07-01

Anticoagulant medications are frequently used to prevent and treat thromboembolic disease. However, the benefits of anticoagulants must be balanced with a careful assessment of the risk of bleeding complications that can ensue from their use. Several bleeding risk scores are available, including the Outpatient Bleeding Risk Index, HAS-BLED, ATRIA, and HEMORR 2 HAGES risk assessment tools, and can be used to help estimate patients' risk for bleeding on anticoagulants. These tools vary by their individual risk components and in how they define and weigh clinical factors. However, it is not yet clear how best to integrate bleeding risk tools into clinical practice. Current bleeding risk scores generally have modest predictive ability and limited ability to predict the most devastating complication of anticoagulation, intracranial hemorrhage. In clinical practice, bleeding risk tools should be paired with a formal determination of thrombosis risk, as their results may be most influential for patients at the lower end of thrombosis risk, as well as for highlighting potentially modifiable risk factors for bleeding. Use of bleeding risk scores may assist clinicians and patients in making informed and individualized anticoagulation decisions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

NOACs replace VKA as preferred oral anticoagulant among new patients: a drug utilization study in 560 pharmacies in The Netherlands.

PubMed

van den Heuvel, J M; Hövels, A M; Büller, H R; Mantel-Teeuwisse, A K; de Boer, A; Maitland-van der Zee, A H

2018-01-01

In 2012, around 400.000 patients in the Netherlands were treated with Vitamin K Antagonists (VKA) for thromboembolic diseases. Since 2011, non-VKA oral anticoagulants (NOACs) are available. NOACs do not require frequent INR monitoring which benefits patients, but also imposes a risk of reduced therapy adherence. The objective of this study is to describe uptake and patient adherence of NOACs in The Netherlands until October 2016. Prescription data for 247.927 patients across 560 pharmacies were used to describe patient profiles, uptake of NOACs among new naive patients and switch between VKA and NOACs, and calculate therapy adherence as the Proportion of Days Covered (PDC). During the studied period the share of NOACs in oral anticoagulants has grown to 57% of prescriptions to new patients. More than 70% of new NOAC users were new naive patients and around 26% switched from VKA. The overall share of NOACs among starters is largest in the group of patients of 50-80 years. Calculated compliance rate for NOAC patients shows that 88% of all users are adherent with a PDC higher than 80%. NOAC have overtaken VKA as the major treatment prescribed to new oral anticoagulant patients, and the number of starters on VKA is decreasing. Patients are generally adherent to NOACs during the implementation phase, the period that the medication is used. Fear for inadherence by itself does not need to be a reason for not prescribing NOACs instead of VKA.

Differentiation of parenteral anticoagulants in the prevention and treatment of venous thromboembolism.

PubMed

Fareed, Jawed; Adiguzel, Cafer; Thethi, Indermohan

2011-03-28

The prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of anticoagulants available. MEDLINE and EMBASE databases were searched to identify relevant original articles. Low-molecular-weight heparins have nearly replaced unfractionated heparin as the gold standard antithrombotic agent. Low-molecular-weight heparins currently available in the US are enoxaparin, dalteparin, and tinzaparin. Each low-molecular-weight heparin is a distinct pharmacological entity with different licensed indications and available clinical evidence. Enoxaparin is the only low-molecular-weight heparin that is licensed for both venous thromboembolism prophylaxis and treatment. Enoxaparin also has the largest body of clinical evidence supporting its use across the spectrum of venous thromboembolism management and has been used as the reference standard comparator anticoagulant in trials of new anticoagulants. As well as novel oral anticoagulant agents, biosimilar and/or generic low-molecular-weight heparins are now commercially available. Despite similar anticoagulant properties, studies report differences between the branded and biosimilar and/or generic agents and further clinical studies are required to support the use of biosimilar low-molecular-weight heparins. The newer parenteral anticoagulant, fondaparinux, is now also licensed for venous thromboembolism prophylaxis in surgical patients and the treatment of acute deep-vein thrombosis; clinical experience with this anticoagulant is expanding. Parenteral anticoagulants should be prescribed in accordance with recommended dose regimens

Time trends in intracranial bleeding associated with direct oral anticoagulants: a 5-year cohort study

PubMed Central

Hogg, Kerstin; Bahl, Bharat; Latrous, Meriem; Scaffidi Argentina, Sarina; Thompson, Jesse; Chatha, Aasil Ayyaz; Castellucci, Lana; Stiell, Ian G.

2015-01-01

Background: Over the past 5 years, dabigatran, rivaroxaban and apixaban were approved for stroke prevention. Phase III studies have shown a lower risk of intracranial bleeding with these direct oral anticoagulants than with warfarin; however, there is a lack of real-life data to validate this. We analyzed time trends in atraumatic intracranial bleeding from 2009 to 2013 among patients prescribed oral anticoagulants and those not prescribed oral anticoagulants. Methods: We used ICD-10-CA (enhanced Canadian version of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems) codes to identify all patients with atraumatic intracranial bleeding who presented to our neurosurgical centre (serving a population of more than 1.2 million). Trained researchers extracted data on anticoagulant medications used in the week before diagnosis of the intracranial bleed. Provincial prescription data for oral anticoagulants were obtained from IMS Brogan CompuScript Market Dynamics. The primary outcome was the time trend in incident intracranial bleeds associated with oral anticoagulation during the period 2009-2013. The secondary outcomes were the time trend in intracranial bleeds not associated with oral anticoagulation and the provincial prescribing patterns for oral anticoagulants during the same period. Results: A total of 2050 patients presented with atraumatic intracranial bleeds during the study period. Of the 371 (18%) prescribed an anticoagulant in the week before presentation, 335 were prescribed an oral anticoagulant. There was an increasing time trend in intracranial bleeding associated with oral anticoagulants (p = 0.009; 6 additional events per year) and in intracranial bleeding not associated with oral anticoagulation (p = 0.06). During 2013, prescriptions for warfarin decreased to 70% of all oral anticoagulant prescriptions in the province, whereas those for dabigatran and rivaroxaban increased to 17% and 12

Early and late effects of coumarin therapy started before percutaneous coronary intervention: Clinical, angiographic and cost-effective outcome of the Balloon Angioplasty and Anticoagulation Study (BAAS).

PubMed

Ten Berg, J M; Kelder, J C; Suttorp, M J; Mast, E G; Bal, E T; Ernst, J M P G; Plokker, H W M

2002-05-01

Coronary angioplasty frequently creates a thrombogenic surface with subsequent mural thrombosis that may lead to acute complications and possibly stimulates the development of restenosis. Whether coumarins can prevent these complications is unclear. In the Balloon Angioplasty and Anticoagulation Study (BAAS), the effect of coumarins started before the procedure on early and late outcome was studied. Patients were randomised to aspirin only or to aspirin plus coumarins. Half of the patients were randomised to undergo six-month angiographic follow-up. Study medication was started one week before coronary angioplasty and the target international normalised ratio (INR) was 2.1-4.8 during angioplasty and six-month follow-up. 'Optimal' anticoagulation was defined as an INR in the target range for at least 70% of the follow-up time. In addition, cost-effectiveness of coumarin treatment was measured. At one year death, myocardial infarction, target-lesion revascularisation and stroke were observed in 14.3% of the 530 patients randomised to aspirin plus coumarin versus in 20.3% of the 528 patients randomised to aspirin alone (relative risk 0.71; 95% CI 0.54-0.93). The incidence of major bleedings and false aneurysms during hospitalisation was 3.2% and 1.0%, respectively, (relative risk 3.39; 95% CI 1.26-9.11). Optimal anticoagulation was an independent predictor of late thrombotic events (relative risk, 0.33; 95% CI, 0.19-0.57). Quantitative coronary analysis was performed of 301 lesions in the ASA group and of 297 lesions in the coumarin group. At six months, the minimal luminal diameter was similar in the ASA and coumarin group. However, optimal anticoagulation was an independent predictor of angiographic outcome at six months. Optimal anticoagulation led to a 0.21 mm (95% CI: 0.05-0.37) larger MLD as compared with suboptimal anticoagulation whereas aspirin use led to a 0.12 mm (95% CI -0.28-0.04) smaller MLD. When including all costs, the savings associated with coumarin

Factor XI as a target for antithrombotic therapy

PubMed Central

Bane, Charles E.; Gailani, David

2014-01-01

Anticoagulants currently used in clinical practice to treat thromboembolic disorders are effective but increase the risk of severe bleeding because they target proteins that are essential for normal coagulation (hemostasis). Drugs with better safety profiles are required for prevention and treatment of thromboembolic disease. Coagulation factor XIa has emerged as a novel target for safer anticoagulant therapy because of its role in thrombosis and its relatively small contribution to hemostasis. PMID:24886766

Adoption of direct oral anticoagulants for stroke prevention in atrial fibrillation.

PubMed

Baker, D; Wilsmore, B; Narasimhan, S

2016-07-01

Direct oral anticoagulants (DOAC) are being increasingly utilised for stroke prevention in atrial fibrillation (AF) and atrial flutter. To analyse the adoption and application of these drugs in a regional hospital inpatient cohort and compare with national prescribing data. Digital medical records identified prescribed anticoagulants for patients admitted with AF and atrial flutter during 2013-2014. Analysis of patient demographics and stroke risk identified trends in prescribing DOAC versus warfarin. For broader comparison, data from the Pharmaceuticals Benefits Scheme were sourced to determine the nation-wide adoption of DOAC. Of the 615 patients identified, 505 (255 in 2013, 250 in 2014) had sufficient records to include in the study. From 2013 to 2014, DOAC prescriptions increased from 9 to 28% (P < 0.001), warfarin and aspirin remained comparatively stable (38-34%, 22-20%), and those prescribed no medication declined (17-8%, P < 0.001). DOAC were prescribed to patients with lower CHA2 DS2 VASc scores than warfarin (3.6 vs 4.4; P = 0.005), lower HAS-BLED scores (1.7 vs 2.3; P < 0.01), higher glomerular filtration rates; 70 vs 63 ml/min; P = 0.002) and younger age (74 vs 77 years; P = 0.006). Nationally, warfarin prescriptions are higher in total numbers but increasing at a slower rate than DOAC, which increased 10-fold (101 158 in 2013, 1 095 985 in 2014). DOAC prescribing grew rapidly from 2013 to 2014, regionally and nationally. Warfarin prescriptions have remained stable, indicating that more patients are being appropriately anticoagulated for AF who previously were not. DOAC were found to be prescribed to patients with lower CHA2 DS2 VASc and HAS-BLED scores, younger age and higher glomerular filtration rates. Aspirin therapy remains over utilised in AF. © 2016 Royal Australasian College of Physicians.

Outcome of Secondary Stroke Prevention in Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants.

PubMed

Nakase, Taizen; Moroi, Junta; Ishikawa, Tatsuya

2018-05-01

Since non-vitamin K antagonist oral anticoagulants (NOACs) were released for clinical use, many studies have investigated its effectiveness in stroke prevention. In this study, to determine whether or not there is a difference in outcome in secondary stroke prevention between warfarin and NOACs, patients with embolic stroke with newly prescribed anticoagulants were prospectively analyzed. Patients with acute ischemic stroke, who newly started anticoagulant therapy, were consecutively asked to participate in this study. Enrolled patients (76.3 ± 11.0 years old) were classified into warfarin (n = 48), dabigatran (n = 73), rivaroxaban (n = 49), and apixaban (n = 65). The outcome in 1 year was prospectively investigated at outpatient clinic or telephone interview. Recurrence of stroke and death was considered as the critical incidence. The prevalence of risk factors was not different among all medicines. Patients with dabigatran showed significantly younger onset age (P < .001: 72.2 years old) and milder neurologic deficits than patients on other medicines (P < .001). Cumulative incident rates were 7.1%, 15.3%, 19.0%, and 29.7% for dabigatran, apixaban, rivaroxaban, and warfarin, respectively. Dabigatran showed relatively better outcome compared with warfarin (P = .069) and rivaroxaban (P = .055). All patients on NOACs presented lower cumulative stroke recurrence compared with warfarin. Even in the situation of secondary stroke prevention, noninferiority of NOACs to warfarin might be demonstrated. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Transurethral ultrasound applicators with dynamic multi-sector control for prostate thermal therapy: In vivo evaluation under MR guidance

PubMed Central

Kinsey, Adam M.; Diederich, Chris J.; Rieke, Viola; Nau, William H.; Pauly, Kim Butts; Bouley, Donna; Sommer, Graham

2008-01-01

The purpose of this study was to explore the feasibility and performance of a multi-sectored tubular array transurethral ultrasound applicator for prostate thermal therapy, with potential to provide dynamic angular and length control of heating under MR guidance without mechanical movement of the applicator. Test configurations were fabricated, incorporating a linear array of two multi-sectored tubular transducers (7.8–8.4 MHz, 3 mm OD, 6 mm length), with three 120° independent active sectors per tube. A flexible delivery catheter facilitated water cooling (100 ml min−1) within an expandable urethral balloon (35 mm long×10 mm diameter). An integrated positioning hub allows for rotating and translating the transducer assembly within the urethral balloon for final targeting prior to therapy delivery. Rotational beam plots indicate ∼90°−100° acoustic output patterns from each 120° transducer sector, negligible coupling between sectors, and acoustic efficiencies between 41% and 53%. Experiments were performed within in vivo canine prostate (n=3), with real-time MR temperature monitoring in either the axial or coronal planes to facilitate control of the heating profiles and provide thermal dosimetry for performance assessment. Gross inspection of serial sections of treated prostate, exposed to TTC (triphenyl tetrazolium chloride) tissue viability stain, allowed for direct assessment of the extent of thermal coagulation. These devices created large contiguous thermal lesions (defined by 52 °C maximum temperature, t43=240 min thermal dose contours, and TTC tissue sections) that extended radially from the applicator toward the border of the prostate (∼15 mm) during a short power application (∼8−16 W per active sector, 8–15 min), with ∼200° or 360° sector coagulation demonstrated depending upon the activation scheme. Analysis of transient temperature profiles indicated progression of lethal temperature and thermal dose contours initially centered

Quality of anticoagulation control: do race and language matter?

PubMed

Bhandari, Vijay Kumar; Wang, Frances; Bindman, Andrew B; Schillinger, Dean

2008-02-01

No studies have evaluated the quality of anticoagulation control among populations characterized by low socioeconomic status, diverse racial and ethnic backgrounds, or limited English proficiency. We conducted a retrospective cohort study to evaluate the effects of race/ethnicity and language on anticoagulation outcomes among patients (N=864) receiving continuous anticoagulation services at a university-affiliated public hospital. White/non-Hispanic patients made up 24%, Asian/Pacific Islanders 33%, Hispanics 22%, African Americans 18%. English (63%), Spanish, (14%), and Cantonese (13%) were the most common languages. Mean time in therapeutic range (TTR) was 43%. After adjustment, TTR was lower for African Americans than for Whites (absolute difference, -8.7%, p< .001) and for Spanish-speaking than for English-speaking Hispanics (absolute difference, -7.2%, p< .05). There were no differences between Asian/Pacific Islanders and Whites, nor between Cantonese-speaking and English-speaking Asian/Pacific Islanders. Future research should examine mechanisms by which race/ethnicity and language affect quality of anticoagulation and evaluate programs to improve treatment in diverse communities.

TH-AB-BRA-11: Using 3D Dosimeters for the Investigation of the Electron Return Effect (ERE) in MR-Guided Radiation Therapy: A Feasibility Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, G; Lee, H; Alqathami, M

Purpose: To demonstrate the capability of 3D radiochromic PRESAGE and Fricke-type dosimeters to measure the influence of magnetic fields on dose distribution, including the electron return effect (ERE), for MR-guided radiation therapy applications. Methods: Short cylindrical 3D dosimeters with PRESAGE and Fricke-type formulations were created in-house prior to irradiations in a 1.5T/7MV MR-linac. Each dosimeter was prepared with a concentric cylindrical air cavity with diameters of 1.5 cm and 2.5 cm, and the diameters of the dosimeters were 7.2 cm and 8.8 cm for PRESAGE and Fricke-type respectively. The dosimeters were irradiated within the bore of the MR-linac with themore » flat face of the dosimeters perpendicular to the magnetic field. Dosimeters were irradiated to approximately 9 Gy and 29 Gy to the center of dosimeters with a 15×15 cm{sup 2} field. The PRESAGE dosimeter was scanned using an optical-CT 2 hours post-irradiation; the Fricke-type dosimeter was immediately imaged with the MR component of the MR-linac post-irradiation. Results: Axial slices of the dose distributions show a clear demonstration of the dose enhancement due to the ERE above the cavity and the region of reduced dose below the cavity. The regions of increased and reduced dose are rotated with respect to the radiation beam axis due to the average directional change of the electrons. Measurements from line profiles show the dose enhanced up to ∼0.5 cm around the cavity by up to a factor of 1.3 and 1.4 for PRESAGE and Fricke-type dosimeters respectively. Conclusion: PRESAGE and Fricke-type dosimeters are able to qualitatively measure the ERE with good agreement with previously published simulation and 2D dosimetry demonstrations of the ERE. Further investigation of these 3D dosimeters as promising candidates for quality assurance of MR-guided radiation therapy systems is encouraged to assess changes in response and measurement accuracy due to the magnetic field.« less

Bleeding events associated with novel anticoagulants: a case series.

PubMed

Mirzaee, Sam; Tran, Tara Thi Thien; Amerena, John

2013-12-01

Until lately warfarin was the only valuable oral anticoagulant in stroke reduction in high risk cases with non valvular atrial fibrillation (NVAF). Although with warfarin the rate of stroke reduced notably, the major concern is the risk of serious bleeding and difficulty of establishing and maintaining the international normalised ratio (INR) within the therapeutic range. With the development of the novel anticoagulants we now have for the first time since the innovation of Warfarin feasible alternatives to it to decrease stroke rates in high risk patients with NVAF. To diminish adverse bleeding events with the novel anticoagulant proper selection of patients prior starting treatment is essential. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Synthesis and biological activity of the novel indanedione anticoagulant rodenticides containing fluorine.

PubMed

Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke

2017-01-02

Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and 1 H nuclear magnetic resonance ( 1 H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity and the feeding indexes of R 1 and R 2 were tested. The result of the experiment proved that the new synthesis of 1, 3 - indan diketone for maternal new anticoagulant rodenticide can replace the current 4 - hydroxyl coumarin as the mother of the second generation anticoagulant rodenticide and 1, 3 - indan diketone for maternal new anticoagulant rodenticides will have a good development prospect.

Comparing intracerebral hemorrhages associated with direct oral anticoagulants or warfarin

PubMed Central

Kurogi, Ryota; Nishimura, Kunihiro; Nakai, Michikazu; Kada, Akiko; Kamitani, Satoru; Nakagawara, Jyoji; Toyoda, Kazunori; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Matsuda, Shinya; Yoshimura, Shinichi; Okuchi, Kazuo; Suzuki, Akifumi; Nakamura, Fumiaki; Onozuka, Daisuke; Ido, Keisuke; Kurogi, Ai; Mukae, Nobutaka; Nishimura, Ataru; Arimura, Koichi; Kitazono, Takanari; Hagihara, Akihito

2018-01-01

Objectives This cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)–associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database. Methods We analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge. Results DOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039). Conclusions This nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies. PMID:29490916

The effect anticoagulation status on geriatric fall trauma patients.

PubMed

Coleman, Julia; Baldawi, Mustafa; Heidt, David

2016-12-01

This research study aims to identify the effect of anticoagulation status on hospital course, complications, and outcomes among geriatric fall trauma patients. The study design is a retrospective cohort study, looking at fall trauma among patients aged 60 to 80 years from 2009 to 2013 at a university hospital in the United States. The statistical analysis, conducted with SPSS software with a threshold for statistical significance of P < .05, was stratified by anticoagulation status and then further by type of anticoagulation (aspirin, warfarin, clopidogrel, enoxaparin, and dipyridamole). Outcomes variables include mortality, length of stay (LOS), intensive care unit (ICU) admission, and complications. The total number of patients included in this study was 1,121. Compared with patients not on anticoagulation, there was a higher LOS among patients on anticoagulation (6.3 ± 6.2 vs 4.9 ± 5.2, P = .001). A higher LOS (7.2 ± 6.8 vs 5.0 ± 5.3, P = .001) and days in the ICU (2.1 ± 5.4 vs 1.1 ± 3.8, P = .010) was observed in patients on warfarin. A higher mortality (7.1% vs 2.8%, P = .013), LOS (6.3 ± 6.2 vs 5.1 ± 5.396, P = .036), and complication rate (49.1 vs 36.7, P = .010) was observed among patients on clopidogrel. In this study, a higher mortality and complication rate were seen among clopidogrel, and a greater LOS and number of days in the ICU were seen in patients on warfarin. These differences are important, as they can serve as a screening tool for triaging the severity of a geriatric trauma patient's condition and complication risk. For patients on clopidogrel, it is essential that these patients are recognized early as high-risk patients who will need to be monitored more closely. For patients on clopidogrel or warfarin, bridging a patient's anticoagulation should be initiated as soon as possible to prevent unnecessary increased LOS. At last, these data also provide support against prescribing patients clopidogrel when other anticoagulation options

Endovascular Therapy is Effective and Safe for Patients with Severe Ischemic Stroke: Pooled Analysis of IMS III and MR CLEAN Data

PubMed Central

Broderick, Joseph P.; Berkhemer, Olvert A.; Palesch, Yuko Y.; Dippel, Diederik W.J.; Foster, Lydia D.; Roos, Yvo B.W.E.M.; van der Lugt, Aad; Tomsick, Thomas A.; Majoie, Charles B.L.M.; van Zwam, Wim H.; Demchuk, Andrew M.; van Oostenbrugge, Robert J.; Khatri, Pooja; Lingsma, Hester F.; Hill, Michael D.; Roozenbeek, Bob; Jauch, Edward C.; Jovin, Tudor G.; Yan, Bernard; von Kummer, Rüdiger; Molina, Carlos A.; Goyal, Mayank; Schonewille, Wouter J.; Mazighi, Mikael; Engelter, Stefan T.; Anderson, Craig S.; Spilker, Judith; Carrozzella, Janice; Ryckborst, Karla J.; Janis, L. Scott; Simpson, Kit

2015-01-01

Background and Purpose We assessed the effect of endovascular treatment in acute ischemic stroke patients with severe neurological deficit (NIHSS ≥20) following a pre-specified analysis plan. Methods The pooled analysis of the IMS III and MR CLEAN trial included participants with an NIHSS ≥20 prior to intravenous (IV) t-PA treatment (IMS III) or randomization (MR CLEAN) who were treated with IV t-PA ≤ 3 hours of stroke onset. Our hypothesis was that participants with severe stroke randomized to endovascular therapy following IV t-PA would have improved 90-day outcome (distribution of modified Rankin scale [mRS] scores), as compared to those who received IV t-PA alone. Results Among 342 participants in the pooled analysis (194 from IMS III, 148 from MR CLEAN), an ordinal logistic regression model showed that the endovascular group had superior 90-day outcome compared to the IV t-PA group (adjusted odds ratio [aOR] 1.78; 95% confidence interval [CI] 1.20-2.66). In the logistic regression model of the dichotomous outcome (mRS 0-2, or ‘functional independence’), the endovascular group had superior outcomes (aOR 1.97; 95% CI 1.09-3.56). Functional independence (mRS ≤2) at 90 days was 25% in the endovascular group as compared to 14% in the IV t-PA group. Conclusions Endovascular therapy following IV t-PA within 3 hours of symptom onset improves functional outcome at 90 days after severe ischemic stroke. PMID:26486865

Dual antiplatelet therapy versus oral anticoagulation plus dual antiplatelet therapy in patients with atrial fibrillation and low-to-moderate thromboembolic risk undergoing coronary stenting: design of the MUSICA-2 randomized trial.

PubMed

Sambola, Antonia; Montoro, J Bruno; Del Blanco, Bruno García; Llavero, Nadia; Barrabés, José A; Alfonso, Fernando; Bueno, Héctor; Cequier, Angel; Serra, Antonio; Zueco, Javier; Sabaté, Manel; Rodríguez-Leor, Oriol; García-Dorado, David

2013-10-01

Oral anticoagulation (OAC) is the recommended therapy for patients with atrial fibrillation (AF) because it reduces the risk of stroke and other thromboembolic events. Dual antiplatelet therapy (DAPT) is required after percutaneous coronary intervention and stenting (PCI-S). In patients with AF requiring PCI-S, the association of DAPT and OAC carries an increased risk of bleeding, whereas OAC therapy or DAPT alone may not protect against the risk of developing new ischemic or thromboembolic events. The MUSICA-2 study will test the hypothesis that DAPT compared with triple therapy (TT) in patients with nonvalvular AF at low-to-moderate risk of stroke (CHADS2 score ≤2) after PCI-S reduces the risk of bleeding and is not inferior to TT for preventing thromboembolic complications. The MUSICA-2 is a multicenter, open-label randomized trial that will compare TT with DAPT in patients with AF and CHADS2 score ≤2 undergoing PCI-S. The primary end point is the incidence of stroke or any systemic embolism or major adverse cardiac events: death, myocardial infarction, stent thrombosis, or target vessel revascularization at 1 year of PCI-S. The secondary end point is the combination of any cardiovascular event with major or minor bleeding at 1 year of PCI-S. The calculated sample size is 304 patients. The MUSICA-2 will attempt to determine the most effective and safe treatment in patients with nonvalvular AF and CHADS2 score ≤2 after PCI-S. Restricting TT for AF patients at high risk for stroke may reduce the incidence of bleeding without increasing the risk of thromboembolic complications. © 2013.

Radiofrequency-enhanced vascular gene transduction and expression for intravascular MR imaging-guided therapy: feasibility study in pigs.

PubMed

Du, Xiangying; Qiu, Bensheng; Zhan, Xiangcan; Kolmakova, Antonina; Gao, Fabao; Hofmann, Lawrence V; Cheng, Linzhao; Chatterjee, Subroto; Yang, Xiaoming

2005-09-01

To evaluate the feasibility of radiofrequency (RF)-enhanced vascular gene transduction and expression by using a magnetic resonance (MR) imaging-heating guidewire as an intravascular heating vehicle during MR imaging-guided therapy. The institutional committee for animal care and use approved the experimental protocol. The study included in vitro evaluation of the use of RF energy to enhance gene transduction and expression in vascular cells, as well as in vivo validation of the feasibility of intravascular MR imaging-guided RF-enhanced vascular gene transduction and expression in pig arteries. For in vitro experiments, approximately 10(4) vascular smooth muscle cells were seeded in each of four chambers of a cell culture plate. Next, 1 mL of a green fluorescent protein gene (gfp)-bearing lentivirus was added to each chamber. Chamber 4 was heated at approximately 41 degrees C for 15 minutes by using an MR imaging-heating guidewire connected to a custom RF generator. At day 6 after transduction, the four chambers were examined and compared at confocal microscopy to determine the efficiency of gfp transduction and expression. For the in vivo experiments, a lentivirus vector bearing a therapeutic gene, vascular endothelial growth factor 165 (VEGF-165), was transferred by using a gene delivery balloon catheter in 18 femoral-iliac arteries (nine artery pairs) in domestic pigs and Yucatan pigs with atherosclerosis. During gene infusion, one femoral-iliac artery in each pig was heated to approximately 41 degrees C with RF energy transferred via the intravascular MR imaging-heating guidewire, while the contralateral artery was not heated (control condition). At day 6, the 18 arteries were harvested for quantitative Western blot analysis to compare VEGF-165 transduction and expression efficiency between RF-heated and nonheated arterial groups. Confocal microscopy showed gfp expression in chamber 4 that was 293% the level of expression in chamber 1 (49.6% +/- 25.8 vs 16

Focused US system for MR imaging-guided tumor ablation.

PubMed

Cline, H E; Hynynen, K; Watkins, R D; Adams, W J; Schenck, J F; Ettinger, R H; Freund, W R; Vetro, J P; Jolesz, F A

1995-03-01

To measure the performance characteristics of a focused ultrasound (US) system for magnetic resonance (MR) imaging-guided tumor ablation. The authors constructed a focused US system for MR imaging-guided tumor ablation. The location of the heated region and thermal dose were monitored with temperature-sensitive MR images obtained in phantoms and rabbit skeletal muscle after application of each sonic pulse. The region heated by the focused ultrasound beam was within 1 mm of that observed on temperature-sensitive fast gradient-echo MR images of in vivo rabbit skeletal muscle. Analysis of heat flow and the rate of coagulation necrosis provided an estimate of the size of the ablated region that was in agreement with experimental findings. MR imaging provides target definition and control for thermal therapy in regions of variable perfusion or in tissues that are not well characterized.

Quality of oral anticoagulation with phenprocoumon in regular medical care and its potential for improvement in a telemedicine-based coagulation service--results from the prospective, multi-center, observational cohort study thrombEVAL.

PubMed

Prochaska, Jürgen H; Göbel, Sebastian; Keller, Karsten; Coldewey, Meike; Ullmann, Alexander; Lamparter, Heidrun; Jünger, Claus; Al-Bayati, Zaid; Baer, Christina; Walter, Ulrich; Bickel, Christoph; ten Cate, Hugo; Münzel, Thomas; Wild, Philipp S

2015-01-23

The majority of studies on quality of oral anticoagulation (OAC) therapy with vitamin K-antagonists are performed with short-acting warfarin. Data on long-acting phenprocoumon, which is frequently used in Europe for OAC therapy and is considered to enable more stable therapy adjustment, are scarce. In this study, we aimed to assess quality of OAC therapy with phenprocoumon in regular medical care and to evaluate its potential for optimization in a telemedicine-based coagulation service. In the prospective observational cohort study program thrombEVAL we investigated 2,011 patients from regular medical care in a multi-center cohort study and 760 patients from a telemedicine-based coagulation service in a single-center cohort study. Data were obtained from self-reported data, computer-assisted personal interviews, and laboratory measurements according to standard operating procedures with detailed quality control. Time in therapeutic range (TTR) was calculated by linear interpolation method to assess quality of OAC therapy. Study monitoring was carried out by an independent institution. Overall, 15,377 treatment years and 48,955 international normalized ratio (INR) measurements were analyzed. Quality of anticoagulation, as measured by median TTR, was 66.3% (interquartile range (IQR) 47.8/81.9) in regular medical care and 75.5% (IQR 64.2/84.4) in the coagulation service (P <0.001). Stable anticoagulation control within therapeutic range was achieved in 63.8% of patients in regular medical care with TTR at 72.1% (IQR 58.3/84.7) as compared to 96.4% of patients in the coagulation service with TTR at 76.2% [(IQR 65.6/84.7); P = 0.001)]. Prospective follow-up of coagulation service patients with pretreatment in regular medical care showed an improvement of the TTR from 66.2% (IQR 49.0/83.6) to 74.5% (IQR 62.9/84.2; P <0.0001) in the coagulation service. Treatment in the coagulation service contributed to an optimization of the profile of time outside therapeutic range, a

Comparison of Direct Oral Anticoagulants and Warfarin in the Treatment of Deep Venous Thrombosis in the Chronic Phase.

PubMed

Wakakura, Shingo; Hara, Fumihiko; Fujino, Tadashi; Hamai, Asami; Ohara, Hiroshi; Kabuki, Takayuki; Harada, Masahiko; Ikeda, Takanori

2018-01-27

We assessed the efficacy and safety of direct oral anticoagulants (DOACs) for the treatment of deep venous thrombosis (DVT) in the chronic phase through comparison with conventional warfarin therapy.A total of 807 consecutive patients who were diagnosed with having DVT in the chronic phase were included (484 patients to warfarin therapy and 323 patients to DOAC therapy). The condition of leg veins was assessed 3 to 6 months after starting the therapies by ultrasound examination. Major bleeding and mortality during the therapies were followed-up.There was no significant difference between the two groups in the thrombosis improvement rate (DOAC group: 91.2% versus warfarin group: 88.9%). There was no significant difference between the two groups in major bleeding (DOAC group: 1.8% versus warfarin group: 1.8%). In patients with active cancer, the DOAC group had a borderline higher thrombosis improvement rate than the warfarin group (92.1% versus 80.0%, P = 0.05). The proportion of major bleeding in the patients with active cancer was slightly higher in the warfarin group than in the DOAC group (4.3% versus 2.8%; P = 0.71). Active cancer was not an independent risk factor for major bleeding and recurrence in the DOAC group (OR 2.68, 95% CI 0.51-14.1; P = 0.24 and OR 0.65, 95% CI 0.20-2.07; P = 0.47).In treatment using oral anticoagulants for DVT in the chronic phase, DOACs exhibited equal efficacy and safety as warfarin did. Particularly DOACs appear to be an attractive therapeutic option for cancer-associated DVT in chronic phase, with relatively low anticipated rates of recurrence and major bleeding.

Liver Cirrhosis in Patients With Atrial Fibrillation: Would Oral Anticoagulation Have a Net Clinical Benefit for Stroke Prevention?

PubMed

Kuo, Ling; Chao, Tze-Fan; Liu, Chia-Jen; Lin, Yenn-Jiang; Chang, Shih-Lin; Lo, Li-Wei; Hu, Yu-Feng; Tuan, Ta-Chuan; Liao, Jo-Nan; Chung, Fa-Po; Chen, Tzeng-Ji; Lip, Gregory Y H; Chen, Shih-Ann

2017-06-23

Patients with liver cirrhosis have been excluded from randomized clinical trials of oral anticoagulation therapy for stroke prevention in atrial fibrillation. We hypothesized that patients with liver cirrhosis would have a positive net clinical benefit for oral anticoagulation when used for stroke prevention in atrial fibrillation. This study used the National Health Insurance Research Database in Taiwan. Among 289 559 atrial fibrillation patients aged ≥20 years, there were 10 336 with liver cirrhosis, and 9056 of them having a CHA 2 DS 2 -VASc score ≥2 were divided into 3 groups, that is, no treatment, antiplatelet therapy, and warfarin. Patients with liver cirrhosis had a higher risk of ischemic stroke (hazard ratio=1.10, P =0.046) and intracranial hemorrhage (hazard ratio=1.20, P =0.043) compared with those without. Among patients with liver cirrhosis, patients taking antiplatelet therapy had a similar risk of ischemic stroke (hazard ratio=1.02, 95%CI=0.88-1.18) compared to those without antithrombotic therapies, but the risk was significantly lowered among warfarin users (hazard ratio=0.76, 95%CI=0.58-0.99). For intracranial hemorrhage, there were no significant differences between those untreated and those taking antiplatelet therapy or warfarin. The use of warfarin was associated with a positive net clinical benefit compared with being untreated or receiving only antiplatelet therapy. For atrial fibrillation patients with liver cirrhosis in the current analysis of an observational study, warfarin use was associated with a lower risk of ischemic stroke and a positive net clinical benefit compared with nontreatment, and thus, thromboprophylaxis should be considered for such patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Treatment of a long-acting anticoagulant rodenticide poisoning cohort with vitamin K1 during the maintenance period

PubMed Central

Long, Jianhai; Peng, Xiaobo; Luo, Yuan; Sun, Yawei; Lin, Guodong; Wang, Yongan; Qiu, Zewu

2016-01-01

Abstract Currently, there are few guidelines for the use of vitamin K1 in the maintenance treatment of long-acting anticoagulant rodenticide (LAAR) poisonings. We explored factors in the treatment of LAAR poisoning during the maintenance period in order to suggest feasible treatment models. Data from 24 cases of anticoagulant rodenticide poisoning in our hospital were collected from January 2013 to May 2016. The patients’ sex, age, coagulation function, total time from poisoning to treatment with vitamin K1 (prehospital time), vitamin K1 sustained treatment time (VKSTT), anticoagulant rodenticide category, and specific poison dosage were collected. Multivariate analysis was used to evaluate the correlation between vitamin K1 dosage and other factors during the maintenance period. Only VKSTT (partial regression coefficient −1.133, 0.59, P = 0.035) had an obvious influence on the therapeutic dose of vitamin K1 required during the maintenance period. After an initial pulse therapy, the bleeding and coagulation functions were stabilized, and the patients were subsequently treated with vitamin K1 during the maintenance period. Over time, the maintenance dose of vitamin K1 (10–120 mg/d, intravenous drip) was gradually decreased and was not related to toxicant concentration. PMID:28002326

Anticoagulant rodenticides and wildlife: Introduction

USGS Publications Warehouse

van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.; van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.

2018-01-01

Rodents have interacted with people since the beginning of systematic food storage by humans in the early Neolithic era. Such interactions have had adverse outcomes such as threats to human health, spoiling and consumption of food sources, damage to human infrastructure and detrimental effects on indigenous island wildlife (through inadvertent anthropogenic assisted introductions). These socio/economic and environmental impacts illustrate the clear need to control populations of commensal rodents. Different methods have been applied historically but the main means of control in the last decades is through the application of rodenticides, mainly anticoagulant rodenticides (ARs) that inhibit blood clotting. The so-called First Generation Anticoagulant Rodenticides (FGARs) proved highly effective but rodents increasingly developed resistance. This led to a demand for more effective alternative compounds and paved the way to the development of Second Generation Anticoagulant Rodenticides (SGARs). These were more acutely toxic and persistent, making them more effective but also increasing the risks of exposure of non-target species and secondary poisoning of predatory species. SGARs often fail the environmental thresholds of different regulatory frameworks because of these negative side-effects, but their use is still permitted because of the overwhelming societal needs for rodent control and the lack of effective alternatives. This book provides a state-of-the-art overview of the scientific advancements in assessment of environmental exposure, effects and risks of currently used ARs. This is discussed in relation to the societal needs for rodent control, including risk mitigation and development of alternatives.

Synthesis and biological activity of the novel indanedione anticoagulant rodenticides containing fluorine

PubMed Central

Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke

2017-01-01

ABSTRACT Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and 1H nuclear magnetic resonance (1H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity and the feeding indexes of R1 and R2 were tested. The result of the experiment proved that the new synthesis of 1, 3 - indan diketone for maternal new anticoagulant rodenticide can replace the current 4 - hydroxyl coumarin as the mother of the second generation anticoagulant rodenticide and 1, 3 - indan diketone for maternal new anticoagulant rodenticides will have a good development prospect. PMID:27759485

Does sex affect anticoagulant use for stroke prevention in nonvalvular atrial fibrillation? The prospective global anticoagulant registry in the FIELD-Atrial Fibrillation.

PubMed

Lip, Gregory Y H; Rushton-Smith, Sophie K; Goldhaber, Samuel Z; Fitzmaurice, David A; Mantovani, Lorenzo G; Goto, Shinya; Haas, Sylvia; Bassand, Jean-Pierre; Camm, Alan John; Ambrosio, Giuseppe; Janský, Petr; Al Mahmeed, Wael; Oh, Seil; van Eickels, Martin; Raatikainen, Pekka; Steffel, Jan; Oto, Ali; Kayani, Gloria; Accetta, Gabriele; Kakkar, Ajay K

2015-03-01

Among patients with atrial fibrillation (AF), women are at higher risk of stroke than men. Using prospective cohort data from a large global population of patients with nonvalvular AF, we sought to identify any differences in the use of anticoagulants for stroke prevention in women and men. This was a prospective multicenter observational registry with 858 randomly selected sites in 30 countries. A total of 17 184 patients with newly diagnosed (≤6 weeks) nonvalvular AF and ≥1 additional investigator-defined stroke risk factor(s) were recruited (March 2010 to June 2013). The main outcome measure was the use of anticoagulants (vitamin K antagonists, factor Xa inhibitors, and direct thrombin inhibitors) for stroke prevention at AF diagnosis. Of 17 184 patients enrolled, 43.8% were women. More women than men were at moderate-to-high risk of stroke (CHADS2 score ≥2: 65.1% versus 54.7%). Rates of anticoagulant use were not different overall (60.9% of men versus 60.8% of women) and in patients with a CHADS2 score ≥2 (adjusted odds ratio for women versus men, 1.00; 95% confidence interval, 0.92-1.09). In patients at low risk (CHA2DS2-VASc of 0 in men and 1 in women), 41.8% of men and 41.1% of women received an anticoagulant. In patients at high risk (CHA2DS2-VASc score ≥2), 35.4% of men and 38.4% of women did not receive an anticoagulant. These contemporary global data show that anticoagulant use for stroke prevention is no different in men and women with nonvalvular AF. Thromboprophylaxis was, however, suboptimal in substantial proportions of men and women, with underuse in those at moderate-to-high risk of stroke and overuse in those at low risk. http://www.clinicaltrials.gov. Unique identifier: NCT01090362. © 2015 American Heart Association, Inc.

Combined anticoagulation and antiplatelet therapy for high-risk patients with atrial fibrillation: a systematic review.

PubMed

Lane, D A; Raichand, S; Moore, D; Connock, M; Fry-Smith, A; Fitzmaurice, D A

2013-07-01

Previous research suggests uncertainty whether or not there is any additional benefit in adding antiplatelet therapy (APT) to anticoagulation therapy (ACT) in patients with high-risk atrial fibrillation (AF) in terms of reduction in vascular events, including stroke. The existing guidelines acknowledge an increased risk of bleeding associated with such a strategy; however, there is no consensus on the treatment pathway. To determine, by undertaking a systematic review, if the addition of APT to ACT is beneficial compared with ACT alone in patients with AF who are considered to be at high risk of thromboembolic events (TEs). Data sources included bibliographic databases {the Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL)], MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, ClinicalTrials.gov, National Institute for Health Research (NIHR) Clinical Research Network Portfolio, Current Controlled Trials (CCT) and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP)}, reference lists from identified systematic reviews and relevant studies, and contact with clinical experts. Searches were from inception to September 2010 and did not use language restrictions or study design filters. Studies of any design were included to evaluate clinical effectiveness, including randomised controlled trials (RCTs), non-randomised comparisons, cohort studies, case series or registries, longitudinal studies, systematic reviews and meta-analyses, and conference abstracts published after 2008. Inclusion criteria consisted of a population with AF, at high-risk of TEs, aged ≥ 18 years, on combined ACT and APT compared with others on ACT alone or ACT plus placebo. Inclusion decisions, assessment of study quality and data extraction were undertaken using methods to minimise bias. Fifty-three publications were included, reporting five RCTs (11 publications), 18 non-randomised comparisons (24 publications) and 18

Perfusion MR Imaging and Proton MR Spectroscopic Imaging in Differentiating Necrotizing Cerebritis from Glioblastoma Multiforme

PubMed Central

Pivawer, Gabriel; Law, Meng; Zagzag, David

2007-01-01

We describe a lesion with the MR imaging characteristics of a glioblastoma mutiforme and demonstrate how perfusion MR imaging and proton MR spectroscopic imaging can be used to differentiate necrotizing cerebritis from what appeared to be a high-grade glioma. A 43 year old woman presented to her physician complaining of progressive visual disturbance and headache for several weeks. Conventional MR imaging demonstrated a parietal peripherally enhancing mass with central necrosis and moderate to severe surrounding T2 hyperintensity suggesting an infiltrating high-grade glioma. However, advanced imaging, including dynamic susceptibility contrast magnetic resonance imaging (DSC MRI) and magnetic resonance spectroscopic imaging (MRSI), suggested a non-neoplastic lesion. The DSC MRI data demonstrated no hyperperfusion within the lesion and surrounding T2 signal abnormality and the MRSI data showed overall decrease in metabolites in this region, except for lactate. Because of the aggressive appearance to the lesion and the patients worsening symptoms, a biopsy was performed. The pathologic diagnosis was necrotizing cerebritis. After the commencement of steroid therapy, imaging findings and patient symptoms improved. This report will review the utility of advanced imaging for differentiating inflammatory from neoplastic appearing lesions on conventional imaging. PMID:17275620

Anticoagulant activity of select dietary supplements.

PubMed

Stanger, Michael J; Thompson, Lauren A; Young, Andrew J; Lieberman, Harris R

2012-02-01

This review considers the potential of certain dietary supplements, including garlic, Ginkgo biloba, ginger, ginseng, fish oil, and vitamin E, to interfere with hemostasis. Dietary supplements are common components of the diet in the United States, with about half the US adult population taking some type of dietary supplement regularly. It has been suggested that some supplements could adversely affect coagulation when taken alone or in combination with antiplatelet medications. Supplements could alter hemostasis by a variety of mechanisms, such as reducing platelet aggregation or inhibiting arachidonic acid, a cellular signaling messenger and inflammatory intermediate. To conduct this review, multiple databases were searched using a variety of search terms to ensure relevant papers were located. Moderate to severe adverse events, such as spinal epidural hematoma, spontaneous intracerebral hemorrhage, retrobulbar hemorrhage, subarachnoid hemorrhage, spontaneous hyphema, and postoperative bleeding, have occasionally been anecdotally associated with consumption of dietary supplements. However, the number of controlled studies in the literature is too limited to demonstrate consistent anticoagulant effects of dietary supplements alone or in combination with drug therapy. © 2012 International Life Sciences Institute.

Modelling the cost-effectiveness of pharmacist-managed anticoagulation service for older adults with atrial fibrillation in Singapore.

PubMed

Chua, Wen Bing Brandon; Cheen, Hua Heng McVin; Kong, Ming Chai; Chen, Li Li; Wee, Hwee Lin

2016-10-01

Background Oral anticoagulation with warfarin is the cornerstone therapy in atrial fibrillation (AF) for stroke prevention. Multi-disciplinary anticoagulation management services have been shown to be cost-effective in the United States, Hong Kong and Thailand, but the findings are not readily generalizable to Singapore's healthcare system. Objective This study aimed to evaluate the cost-effectiveness of pharmacist-managed anticoagulation clinic (ACC) compared with usual care (UC) for the management of older adults with AF receiving oral anticoagulation with warfarin. Setting Pharmacist-managed ACC in an academic medical centre. Method A Markov model with 3-month cycle length and 30-year time horizon compared costs and quality-adjusted life-years (QALYs) of ACC and UC from the patient's and healthcare provider's perspectives. Four pathways based on time in therapeutic range (TTR) were: ACC TTR < 70 %, ACC TTR ≥ 70 %, UC TTR < 70 % and UC TTR ≥ 70 %. A hypothetical cohort of 70-year-old Singaporean AF patients receiving warfarin was utilised. Local data from national disease registries, patient surveys and hospital databases were used. When local data was not available, published studies on Asian populations were utilized when available. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to account for uncertainties. Costs and QALYs were discounted annually by 3 %. Main outcome measure Costs and QALYs of ACC and UC. Results Pharmacist-managed ACC was found to dominate UC in all comparisons. It improved effectiveness by 0.19 and 0.13 QALYs at TTR < 70 % and TTR ≥ 70 % respectively compared with UC. From the patient's perspective, ACC reduced costs by SG$1222.67 (€1110.24) for TTR < 70 % and SG$1008.16 (€915.46) for TTR ≥ 70 %. Similar trends were observed from the healthcare provider's perspective, with ACC reducing costs by SG$1444.79 (€1311.94) for TTR < 70 % and SG$1269.17 (€1152.46) for

Delay in onset of metabolic alkalosis during regional citrate anti-coagulation in continuous renal replacement therapy with calcium-free replacement solution.

PubMed

See, Kay Choong; Lee, Margaret; Mukhopadhyay, Amartya

2009-01-01

Regional citrate anti-coagulation for continuous renal replacement therapy chelates calcium to produce the anti- coagulation effect. We hypothesise that a calcium-free replacement solution will require less citrate and produce fewer metabolic side effects. Fifty patients, in a Medical Intensive Care Unit of a tertiary teaching hospital (25 in each group), received continuous venovenous hemofiltration using either calcium-containing or calcium-free replacement solutions. Both groups had no significant differences in filter life, metabolic alkalosis, hypernatremia, hypocalcemia, and hypercalcemia. However, patients using calcium-containing solution developed metabolic alkalosis earlier, compared to patients using calcium-free solution (mean 24.6 hours,CI 0.8-48.4 vs. 37.2 hours, CI 9.4-65, P = 0.020). When calcium-containing replacement solution was used, more citrate was required (mean 280 ml/h, CI 227.2-332.8 vs. 265 ml/h, CI 203.4-326.6, P = 0.069), but less calcium was infused (mean 21.2 ml/h, CI 1.2-21.2 vs 51.6 ml/h, CI 26.8-76.4, P < or = 0.0001).

A Case of Acute Budd-Chiari Syndrome Complicating Primary Antiphospholipid Syndrome Presenting as Acute Abdomen and Responding to Tight Anticoagulant Therapy.

PubMed

Chinen, Naofumi; Koyama, Yasushi; Sato, Shinji; Suzuki, Yasuo

2016-01-01

A 34-year-old woman with primary antiphospholipid syndrome was admitted to the Gastroenterology Department of our hospital with fever, acute abdomen, watery diarrhea, and extremely high levels of inflammatory parameters. She had a history of left lower limb deep vein thrombosis and pulmonary embolism and was taking warfarin potassium. Acute gastroenteritis was suspected and an antibiotic was administered, but symptoms progressed. Abdominal ultrasonography showed occlusion of the left hepatic vein and the middle hepatic vein and her D-dimer level was high. Accordingly, Budd-Chiari syndrome was diagnosed and high-dose intravenous infusion of heparin was initiated. Her abdominal symptoms improved and the levels of inflammatory parameters and D-dimer decreased rapidly. It is known that antiphospholipid syndrome can be complicated by Budd-Chiari syndrome that usually occurs as subacute or chronic onset, but acute onset is rare. It is difficult to diagnose acute Budd-Chiari syndrome complicating antiphospholipid syndrome and this complication generally has a poor outcome. However, the present case can get early diagnosis and successful treatment with tight anticoagulant therapy.

Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

PubMed

Sieg, Adam; Mardis, B Andrew; Mardis, Caitlin R; Huber, Michelle R; New, James P; Meadows, Holly B; Cook, Jennifer L; Toole, J Matthew; Uber, Walter E

2015-01-01

Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation.

Warfarin Safety: A Cross-Sectional Study of the Factors Associated with the Consumption of Medicinal Plants in a Brazilian Anticoagulation Clinic.

PubMed

Leite, Paula Mendonça; de Freitas, Aline A; Mourão, Aline de O Magalhães; Martins, Maria A P; Castilho, Rachel O

2018-06-01

The aim of this study was to analyze factors associated with the consumption of medicinal plants by patients being treated with warfarin in a Brazilian anticoagulation clinic and to study the safety of medicinal plant use in patients on warfarin therapy. The study was performed as an observational cross-sectional analysis. Study participants were outpatients on long-term warfarin therapy for at least 2 months for atrial fibrillation or prosthetic cardiac valves. Interviews were carried out concerning information about the habits of medicinal herb consumption, and logistic regression analysis was performed to identify factors associated with the consumption of herbs. The scientific names of the medicinal plants were identified to search for information on the effects on the hemostasis of the interactions between the medicinal herbs reported and warfarin. The mean age of the 273 patients included was 60.8 years; 58.7% were women. Medicinal plants were used by 67% of the participants. No association between demographic and clinical data and the use of medicinal plants was identified. Patients reported a total of 64 different plants, primarily consumed in the form of tea. The plants were mainly used to treat respiratory tract and central nervous system disorders. About 40% of the plants cited have been reported to potentially interfere with the anticoagulation therapy, principally by potentiating the effects of warfarin, which could, increase the risk of bleeding. The use of medicinal plants was highly common and widespread in patients receiving warfarin as an anticoagulation therapy. Univariate analysis of variables associated with the consumption of herbs showed no statistically significant difference in the consumption of medicinal plants for any of the sociodemographic and clinical data. The medicinal plants that were reportedly consumed by the patients could affect hemostasis. This study reinforces the need for further studies evaluating the habits of patients

Therapy response assessment after radioembolization of patients with hepatocellular carcinoma--comparison of MR imaging with gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid and gadobutrol.

PubMed

Schelhorn, Juliane; Best, Jan; Reinboldt, Marcus P; Gerken, Guido; Ruhlmann, Marcus; Lauenstein, Thomas C; Antoch, Gerald; Kinner, Sonja

2015-07-01

To compare the utility of gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA), a liver-specific magnetic resonance (MR) imaging contrast agent, versus gadobutrol for treatment response evaluation of hepatocellular carcinoma (HCC) after radioembolization. This prospective study included 50 patients with HCC undergoing radioembolization. All patients underwent contrast-enhanced computed tomography (CT) and MR imaging with gadobutrol and Gd-EOB-DTPA on 2 consecutive days before radioembolization and 30 days, 90 days, 180 days, and 270 days after radioembolization. The standard of reference indicating tumor progression was CT combined with either α-fetoprotein or γ-glutamyltransferase. Gadobutrol-enhanced MR imaging, Gd-EOB-DTPA-enhanced MR imaging without late phase imaging (Gd-EOB-DTPA-), and Gd-EOB-DTPA-enhanced MR imaging with late phase imaging (Gd-EOB-DTPA+) were evaluated by 2 radiologists in consensus using a 4-point scale: 1 = definitely no tumor progression; 2 = probably no tumor progression; 3 = probably tumor progression; 4 = definitely tumor progression. Diagnostic accuracy was assessed with receiver operating characteristic analysis. Tumor progression was detected in 14 of 82 study visits according to the reference standard. Pairwise comparison of the area under the curve showed a tendency toward a larger area under the curve for Gd-EOB-DTPA+ compared with gadobutrol (P = .056). Sensitivity and specificity were higher in Gd-EOB-DTPA+ (0.929 and 0.971) than in Gd-EOB-DTPA- (0.786 and 0.941) or gadobutrol (0.643 and 0.956). In 2 cases, tumor progression was detected by Gd-EOB-DTPA+ and by an increase in α-fetoprotein, but not by CT, gadobutrol, or Gd-EOB-DTPA-. Gd-EOB-DTPA+ MR imaging was not inferior to gadobutrol-enhanced MR imaging in therapy response evaluation after radioembolization and may allow a more accurate detection of early HCC recurrence in single cases. Copyright © 2015 SIR. Published by Elsevier Inc. All rights

Anticoagulant and antiplatelet therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.

PubMed

Goto, Koji; Nakai, Kentaro; Shizuta, Satoshi; Morimoto, Takeshi; Shiomi, Hiroki; Natsuaki, Masahiro; Yahata, Mitsuhiko; Ota, Chihiro; Ono, Koh; Makiyama, Takeru; Nakagawa, Yoshihisa; Furukawa, Yutaka; Kadota, Kazushige; Takatsu, Yoshiki; Tamura, Takashi; Takizawa, Akinori; Inada, Tsukasa; Doi, Osamu; Nohara, Ryuji; Matsuda, Mitsuo; Takeda, Teruki; Kato, Masayuki; Shirotani, Manabu; Eizawa, Hiroshi; Ishii, Katsuhisa; Lee, Jong-Dae; Takahashi, Masaaki; Horie, Minoru; Takahashi, Mamoru; Miki, Shinji; Aoyama, Takeshi; Suwa, Satoru; Hamasaki, Shuichi; Ogawa, Hisao; Mitsudo, Kazuaki; Nobuyoshi, Masakiyo; Kita, Toru; Kimura, Takeshi

2014-07-01

The prevalence, intensity, safety, and efficacy of oral anticoagulation (OAC) in addition to dual antiplatelet therapy (DAPT) in "real-world" patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not yet been fully evaluated. In the Coronary REvascularization Demonstrating Outcome Study in Kyoto registry cohort-2, a total of 1,057 patients with AF (8.3%) were identified among 12,716 patients undergoing first PCI. Cumulative 5-year incidence of stroke was higher in patients with AF than in no-AF patients (12.8% vs 5.8%, p <0.0001). Although most patients with AF had CHADS2 score ≥2 (75.2%), only 506 patients (47.9%) received OAC with warfarin at hospital discharge. Cumulative 5-year incidence of stroke in the OAC group was not different from that in the no-OAC group (13.8% vs 11.8%, p = 0.49). Time in therapeutic range (TTR) was only 52.6% with an international normalized ratio of 1.6 to 2.6, and only 154 of 409 patients (37.7%) with international normalized ratio data had TTR ≥65%. Cumulative 5-year incidence of stroke in patients with TTR ≥65% was markedly lower than that in patients with TTR <65% (6.9% vs 15.1%, p = 0.01). In a 4-month landmark analysis in the OAC group, there was a trend for higher cumulative incidences of stroke and major bleeding in the on-DAPT (n = 286) than in the off-DAPT (n = 173) groups (15.1% vs 6.7%, p = 0.052 and 14.7% vs 8.7%, p = 0.10, respectively). In conclusion, OAC was underused and its intensity was mostly suboptimal in real-world patients with AF undergoing PCI, which lead to inadequate stroke prevention. Long-term DAPT in patients receiving OAC did not reduce stroke incidence. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 1

PubMed Central

Diener, Hans-Christoph; Aisenberg, James; Ansell, Jack; Atar, Dan; Breithardt, Günter; Eikelboom, John; Ezekowitz, Michael D.; Granger, Christopher B.; Halperin, Jonathan L.; Hohnloser, Stefan H.; Hylek, Elaine M.; Kirchhof, Paulus; Lane, Deirdre A.; Verheugt, Freek W.A.; Veltkamp, Roland; Lip, Gregory Y.H.

2017-01-01

Patients with atrial fibrillation (AF) have a high risk of stroke and mortality, which can be considerably reduced by oral anticoagulants (OAC). Recently, four non-vitamin-K oral anticoagulants (NOACs) were compared with warfarin in large randomized trials for the prevention of stroke and systemic embolism. Today's clinician is faced with the difficult task of selecting a suitable OAC for a patient with a particular clinical profile or a particular pattern of risk factors and concomitant diseases. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. NOACs for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In the first of a two-part review, we discuss the choice of NOAC for stroke prevention in the following subgroups of patients with AF: (i) stable coronary artery disease or peripheral artery disease, including percutaneous coronary intervention with stenting and triple therapy; (ii) cardioversion, ablation and anti-arrhythmic drug therapy; (iii) mechanical valves and rheumatic valve disease, (iv) patients with time in therapeutic range of >70% on warfarin; (v) patients with a single stroke risk factor (CHA2DS2VASc score of 1 in males, 2 in females); and (vi) patients with a single first episode of paroxysmal AF. Although there are no major differences in terms of efficacy and safety between the NOACs for some clinical scenarios, in others we are able to suggest that particular drugs and/or doses be prioritized for anticoagulation. PMID:26848149

Prostate thermal therapy with catheter-based ultrasound devices and MR thermal monitoring

NASA Astrophysics Data System (ADS)

Diederich, Chris J.; Nau, Will H.; Kinsey, Adam; Ross, Tony; Wootton, Jeff; Juang, Titania; Butts-Pauly, Kim; Ricke, Viola; Liu, Erin H.; Chen, Jing; Bouley, Donna M.; Van den Bosch, Maurice; Sommer, Graham

2007-02-01

Four types of transurethral applicators were devised for thermal ablation of prostate combined with MR thermal monitoring: sectored tubular transducer devices with directional heating patterns; planar and curvilinear devices with narrow heating patterns; and multi-sectored tubular devices capable of dynamic angular control without applicator movement. These devices are integrated with a 4 mm delivery catheter, incorporate an inflatable cooling balloon (10 mm OD) for positioning within the prostate and capable of rotation via an MR-compatible motor. Interstitial devices (2.4 mm OD) have been developed for percutaneous implantation with directional or dynamic angular control. In vivo experiments in canine prostate under MR temperature imaging were used to evaluate the heating technology and develop treatment control strategies. MR thermal imaging in a 0.5 T interventional MRI was used to monitor temperature and thermal dose in multiple slices through the target volume. Sectored tubular, planar, and curvilinear transurethral devices produce directional coagulation zones, extending 15-20 mm radial distance to the outer prostate capsule. Sequential rotation and modulated dwell time can conform thermal ablation to selected regions. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the gland in short treatment times without applicator manipulation. Interstitial implants with directional devices can be used to effectively ablate the posterior peripheral zone of the gland while protecting the rectum. The MR derived 52 °C and lethal thermal dose contours (t 43=240 min) allowed for real-time control of the applicators and effectively defined the extent of thermal damage. Catheter-based ultrasound devices, combined with MR thermal monitoring, can produce relatively fast and precise thermal ablation of prostate, with potential for treatment of cancer or BPH.

Economic evaluation of prescribing conventional and newer oral anticoagulants in older adults.

PubMed

Hasan, Syed Shahzad; Kow, Chia Siang; Curley, Louise E; Baines, Darrin L; Babar, Zaheer-Ud-Din

2018-05-09

Anticoagulants refer to a variety of agents that inhibit one or more steps in the coagulation cascade. Generally, clinical conditions that require the prescribing of an oral anticoagulant increase in frequency with age. However, a major challenge of anticoagulation use among older patients is that this group of patients also experience the highest bleeding risk. To date, economic evaluation of prescribing of anticoagulants that includes the novel or newer oral anticoagulants (NOACs) in older adults has not been conducted and is warranted. Areas covered: A review of articles that evaluated the cost of prescribing conventional (e.g. vitamin K antagonists) and NOACs (e.g. direct thrombin inhibitors and direct factor Xa inhibitors) in older adults. Expert commentary: While the use of NOACs significantly increases the cost of the initial treatment for thromboembolic disorders, they are still considered cost-effective relative to warfarin since they offer reduced risk of intracranial haemorrhagic events. The optimum anticoagulation with warfarin can be achieved by providing specialised care; clinics managed by pharmacists have been shown to be cost-effective relative to usual care. There are suggestions that genotyping the CYP2C9 and VKORC1 genes is useful for determining a more appropriate initial dose and thereby increasing the effectiveness and safety of warfarin.

Clinical considerations on the posology of direct oral anticoagulants.

PubMed

Sáez-Peñataro, J; Avendaño-Solá, C; González-Juanatey, J R

2016-10-01

The efficacy of dicoumarin anticoagulants has been shown in patients with nonvalvular atrial fibrillation. However, they have drawbacks such as the need to adjust the dosage and the interaction with drugs and food. Direct oral anticoagulants are an effective and safe alternative and have a less complicated clinical management. There is considerable debate on the selection criteria for the posology regimens of direct oral anticoagulants. The differences among them and their administration regimens have raised questions about the clinical, pharmacokinetic and pharmacodynamic selection criteria that support the posology. This review critically analyses the available evidence and its impact on the final selection of the dosage regimen. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Evaluation of bleeding in patients receiving direct oral anticoagulants

PubMed Central

Hellenbart, Erika L; Faulkenberg, Kathleen D; Finks, Shannon W

2017-01-01

Direct oral anticoagulants (DOACs) are recognized by evidence-based treatment guidelines as the first-line option for the treatment of venous thromboembolism and prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. As use of these anticoagulants has become favored over the past several years, reported bleeding-related adverse drug events with these agents has increased. In randomized clinical trials, all DOACs have a reduced risk for intracranial hemorrhage, while major and other bleeding results have varied among the agents compared to vitamin K antagonists. We have reviewed the bleeding incidence and severity from randomized and real-world data in patients receiving DOACs in an effort to provide the clinician with a critical review of bleeding and offer practical considerations for avoiding adverse events with these anticoagulants. PMID:28860793

MO-FG-BRC-01: MR-Guided Radiation Therapy with Gadolinium Nanoparticles: From Chalkboard to First Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sancey, L.

2016-06-15

Experimental research in medical physics has expanded the limits of our knowledge and provided novel imaging and therapy technologies for patients around the world. However, experimental efforts are challenging due to constraints in funding, space, time and other forms of institutional support. In this joint ESTRO-AAPM symposium, four exciting experimental projects from four different countries are highlighted. Each project is focused on a different aspect of radiation therapy. From the USA, we will hear about a new linear accelerator concept for more compact and efficient therapy devices. From Canada, we will learn about novel linear accelerator target design and themore » implications for imaging and therapy. From France, we will discover a mature translational effort to incorporate theranostic nanoparticles in MR-guided radiation therapy. From Germany, we will find out about a novel in-treatment imaging modality for particle therapy. These examples of high impact, experimental medical physics research are representative of the diversity of such efforts that are on-going around the globe. J. Robar, Research is supported through collaboration with Varian Medical Systems and Brainlab AGD. Westerly, This work is supported by the Department of Radiation Oncology at the University of Colorado School of Medicine. COI: NONEK. Parodi, Part of the presented work is supported by the DFG (German Research Foundation) Cluster of Excellence MAP (Munich-Centre for Advanced Photonics) and has been carried out in collaboration with IBA.« less

Radiofrequency Ablation, MR Thermometry, and High-Spatial-Resolution MR Parametric Imaging with a Single, Minimally Invasive Device.

PubMed

Ertürk, M Arcan; Sathyanarayana Hegde, Shashank; Bottomley, Paul A

2016-12-01

Purpose To develop and demonstrate in vitro and in vivo a single interventional magnetic resonance (MR)-active device that integrates the functions of precise identification of a tissue site with the delivery of radiofrequency (RF) energy for ablation, high-spatial-resolution thermal mapping to monitor thermal dose, and quantitative MR imaging relaxometry to document ablation-induced tissue changes for characterizing ablated tissue. Materials and Methods All animal studies were approved by the institutional animal care and use committee. A loopless MR imaging antenna composed of a tuned microcable either 0.8 or 2.2 mm in diameter with an extended central conductor was switched between a 3-T MR imaging unit and an RF power source to monitor and perform RF ablation in bovine muscle and human artery samples in vitro and in rabbits in vivo. High-spatial-resolution (250-300-μm) proton resonance frequency shift MR thermometry was interleaved with ablations. Quantitative spin-lattice (T1) and spin-spin (T2) relaxation time MR imaging mapping was performed before and after ablation. These maps were compared with findings from gross tissue examination of the region of ablated tissue after MR imaging. Results High-spatial-resolution MR imaging afforded temperature mapping in less than 8 seconds for monitoring ablation temperatures in excess of 85°C delivered by the same device. This produced irreversible thermal injury and necrosis. Quantitative MR imaging relaxation time maps demonstrated up to a twofold variation in mean regional T1 and T2 after ablation versus before ablation. Conclusion A simple, integrated, minimally invasive interventional probe that provides image-guided therapy delivery, thermal mapping of dose, and detection of ablation-associated MR imaging parametric changes was developed and demonstrated. With this single-device approach, coupling-related safety concerns associated with multiple conductor approaches were avoided. © RSNA, 2016 Online

Clinical Relevance of Anticoagulation and Dual Antiplatelet Therapy to the Outcomes of Patients With Atrial Fibrillation and Recent Percutaneous Coronary Intervention With Stent.

PubMed

De Vecchis, Renato; Cantatrione, Claudio; Mazzei, Damiana

2016-02-01

Chronic atrial fibrillation (AF), coexisting with a history of recent coronary angioplasty with stent (PCI-S), represents an encoded indication for oral anticoagulation (OAC) with warfarin plus dual antiplatelet therapy (DAPT). Using a retrospective cohort study, we determined the respective impacts on cardiovascular outcomes of three different pharmacologic regimens, i.e., triple therapy (TT) with warfarin + clopidogrel and aspirin, dual therapy (DT) with warfarin + clopidogrel or aspirin, and DAPT with clopidogrel + aspirin. Outcomes of interest were all-cause mortality, ischemic cardiac events, ischemic cerebral events, and bleeding events. The inclusion criterion was the coexistence of an indication for OAC (e.g., chronic AF) with an indication for DAPT due to recent PCI-S. Among the 98 patients enrolled, 48 (49%), 31 (31.6%), and 19 (19.4%) patients were prescribed TT, DT, and DAPT, respectively. Throughout a mean follow-up of 378 ± 15.7 days, there were no significant differences between the three regimens for all abovementioned outcomes. In particular, the total frequency of major bleeding was similar in the three groups: five cases (10.4%) in TT, one case (3.22%) in DT and no case in DAPT groups (Chi-square test, P = 0.1987). TT, DT and DAPT displayed similar efficacy and safety. Although the superiority of OAC vs. DAPT for stroke prevention in AF patients has been demonstrated by previous randomized trials, a smaller frequency of high thromboembolic risks' features in DAPT group of the present study may have prevented the observation of a higher incidence of ischemic stroke in this group.

MR contrast media for myocardial viability, microvascular integrity and perfusion.

PubMed

Saeed, M; Wendland, M F; Watzinger, N; Akbari, H; Higgins, C B

2000-06-01

Cardiovascular imaging requires an appreciation of rapidly evolving MR imaging sequences as well as careful utilization of intravascular, extracellular and intracellular MR contrast media. At the present time, clinical studies are restricted to the use of extracellular MR contrast media. MR imaging has the potential to noninvasively measure multiple parameters of the cardiovascular system in a single imaging session. Recent advances in fast and ultrafast MR imaging have considerably enhanced the capability of this technique, beyond the assessment of left ventricular wall motion and morphology into visualization of the coronary arteries and measurement of blood flow. During the course of the last several years, multiple strategies for imaging viable myocardium have been developed and validated using MR contrast media. Contrast enhanced dynamic MR imaging provides information regarding microvascular integrity and perfusion. Because these information can be provided noninvasively by MR imaging, repeated measurements can be performed in longitudinal studies to monitor the progression or regression of myocardial injury. Similar studies are needed to examine the effects of newly developed cardioprotective therapeutics. Development of suitable intravascular MR contrast medium may be essential for visualization of the coronary arteries and interventional therapies. MR imaging may emerge as one-stop-shop for evaluating the heart and coronary system. This capability will make MR imaging cost-effective in the first decade of this millennium.

Comparison of pre-filter and post-filter ionised calcium monitoring in continuous veno-venous hemodiafiltration (CVVHD-F) with citrate anti-coagulation.

PubMed

Brain, Matthew J; Roodenburg, Owen S; McNeil, John

2017-01-01

It is widespread practice during citrate anticoagulated renal replacement therapy to monitor circuit ionised calcium (iCa2+) to evaluate the effectiveness of anticoagulation. Whether the optimal site to sample the blood path is before or after the haemofilter is a common question. Using a prospectively collected observational dataset from intensive care patients receiving pre-dilution continuous veno-venous haemodiafiltration (CVVHD-F) with integrated citrate anticoagulation we compared paired samples of pre and post filter iCa2+ where the target range was 0.3-0.5 mmol.L-1 as well as concurrently collected arterial iCa2+. Two nested mixed methods linear models were fitted to the data describing post vs pre filter iCa2+, and the relationship of pre, post and arterial samples. An 11 bed general intensive care unit. 450 grouped samples from 152 time periods in seven patients on CRRT with citrate anticoagulation. The relationship of post to pre-filter iCa2+ was not 1:1 with post = 0.082 + 0.751 x pre-filter iCa2+ (95% CI intercept: 0.015-0.152, slope 0.558-0.942). Variation was greatest between patients rather than between circuits within the same patient or citrate dose. Compared to arterial iCa2+ there was no significant difference between pre and post-filter sampling sites (F-value 0.047, p = 0.827). These results demonstrate that there is minimal difference between pre and post filter samples for iCa2+ monitoring of circuit anticoagulation in citrate patients relative to the arterial iCa2+ in CVVHD-F however compared to pre-filter sampling, post filter sampling has a flatter response and greater variation.

Does IV contrast extravasation on CT in anticoagulant-related rectus sheath and iliopsoas hematoma predict hematoma expansion and patient outcomes?

PubMed

Landecy, Marie; Paquette, Brice; Revel, Lucie; Behr, Julien; Badet, Nicolas; Delabrousse, Eric

2016-11-01

(p = 0.9). Among anticoagulant therapy, only vitamin K antagonist therapy was statistically associated with surgery (p = 0.04). CT extravasation of contrast material in IP and RS hematoma does not appear to be related with clinical criteria of severity, and therefore should not be solely considered as a radiological decision criteria.

Antioxidant and anticoagulant activity of polyphenol and polysaccharides from fermented Sargassum sp.

PubMed

Shobharani, P; Nanishankar, V H; Halami, P M; Sachindra, N M

2014-04-01

The current investigation was carried out with an objective of determining the structural characteristic of polysaccharides extracted from fermented Sargassum sp. to be used as potent natural heparin substitute anticoagulant compound. Sargassum sp. fermented with marine lactic acid bacteria was initially subjected to ethanol precipitation for the recovery of bioactive compounds. Antioxidant activity was maximum in the soluble fraction whereas anticoagulant activity was observed to be high in the precipitate which correlated with the increased polyphenols and total sugars respectively. The precipitate was purified by anion exchange chromatography and the fractions collected were analyzed for total sugars and anticoagulant activity. There was 2.6-3.9-folds increase in anticoagulant activity in the final purified fractions, with a maximum activity in case of sample fermented with Enterococcus faecium (6.7±0.22 IU/mg). Structural elucidation of potential anticoagulant polysaccharide by Fourier Transform Infrared Spectroscopy (FT-IR) and Nuclear Magnetic Resonance (NMR) analysis indicated the presence of alginate rich in mannuronic acid. Copyright © 2014 Elsevier B.V. All rights reserved.

Meta-analysis of CHADS2 versus CHA2DS2-VASc for predicting stroke and thromboembolism in atrial fibrillation patients independent of anticoagulation.

PubMed

Zhu, Wen-Gen; Xiong, Qin-Mei; Hong, Kui

2015-02-01

Two validated scoring systems for predicting embolic risk, CHADS2 and CHA2DS2-VASc, contribute to optimizing antithrombotic prescription practices in patients who have atrial fibrillation. However, data about anticoagulated patients are sparse. We compared CHADS2 and CHA2DS2-VASc, in terms of their predictive risk evaluation, in patients with atrial fibrillation who were and were not taking anticoagulants. We systematically searched the Cochrane Library, PubMed, and Embase databases for studies of the comparative diagnostic performance of CHADS2 and CHA2DS2-VASc. We identified 12 cohort studies for meta-analysis. With regard to the occurrence of cardiovascular events individually, patients with CHA2DS2-VASc scores ≥2 have a greater risk of stroke (risk ratio [RR]=5.15; 95% confidence interval [CI], 3.85-6.88; P <0.00001) and thromboembolism (RR=5.96; 95% CI, 5.50-6.45; P <0.00001) (P diff=0.34) than do patients with CHA2DS2-VASc scores <2, independent of anticoagulation therapy (RR=5.76; 95% CI, 5.23-6.35; P <0.00001 in anticoagulated patients; and RR=6.12; 95% CI, 5.40-6.93; P <0.00001 in patients not taking anticoagulants; P diff=0.45). The pooled RR estimates indicate an approximate 6-fold increase in the risk of endpoint events in patients with CHA2DS2-VASc scores ≥2 (RR=5.90; 95% CI, 5.46-6.37; P <0.0001). These results clearly indicate the discriminative capacity of the CHA2DS2-VASc score for stroke, thromboembolic events, or both, independent of optimal anticoagulation. The CHA2DS2-VASc score enables the identification of patients who are at genuinely high risk and can direct the selection of appropriate therapeutic approaches.

Intracranial hemorrhage in anticoagulated patients with mild traumatic brain injury: significant differences between direct oral anticoagulants and vitamin K antagonists.

PubMed

Cipriano, Alessandro; Pecori, Alessio; Bionda, Alessandra Eugenia; Bardini, Michele; Frassi, Francesca; Leoli, Francesco; Lami, Valentina; Ghiadoni, Lorenzo; Santini, Massimo

2018-03-08

Prognosis after mild traumatic brain injury (MTBI) on oral anticoagulant therapy (OAT) is uncertain. We evaluated the rate of immediate and delayed traumatic intracranial hemorrhage (ICH) comparing vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs) and the safety of a clinical management protocol. In this single-center prospective observational study, we enrolled 220 patients on OAT with MTBI. After a first negative CT scan, asymptomatic patients underwent a close neurological observation; if neurologically stable, they were discharged without a second CT scan and followed up for 1 month. Out of the 220 patients, 206 met the inclusion criteria. 23 of them (11.2%) had a positive first CT scan for ICH. Only 1 (0.5%, 95% CI 0.0-1.4%) died because of ICH; no one required neurosurgical intervention. The observed prevalence rate of immediate ICH resulted statistically higher in VKAs-treated patients compared to those treated with DOACs (15.7 vs. 4.7%, RR 3.34, 95% CI 1.18-9.46, P < 0.05). In the 1-month follow-up, 5 out of the 183 patients with a negative CT scan were lost. Out of the remaining 178 patients, only 3 showed a delayed ICH (1.7%, 95% CI 0.0-3.6%), 1 of them died (0.6%, 95% CI 0.5-1.7%) and the others did not require neurosurgical intervention. DOACs resulted safer than VKAs also in the setting of MTBI. In our observation, the rate of delayed hemorrhage was relatively low. Patients presenting with a negative first CT scan and without neurological deterioration could be safely discharged after a short period of in-ward observation with a low rate of complications and without a second CT scan.

Lupus anticoagulant, anticardiolipin antibodies, and human immunodeficiency virus in haemophilia.

PubMed Central

Cohen, H; Mackie, I J; Anagnostopoulos, N; Savage, G F; Machin, S J

1989-01-01

The prevalence of lupus anticoagulant, using the dilute Russell's viper venom time (DRVT), was determined in 22 patients with mild to severe haemophilia A to see if there was any association with the presence of viral disease. Twelve haemophiliacs (58%) were lupus anticoagulant positive, with a mean patient:control ratio of 1.24 (range 1.15-1.52, normal range 0.84-1.06 which partially corrected with lysed, washed platelets). Nine of these patients were IgG or IgM, or both, anticardiolipin antibody positive and nine were human immunodeficiency virus (HIV) antibody positive, but associations between lupus anticoagulant, anticardiolipin antibodies, and HIV antibody positivity were not significant. Mixing studies of normal plasma and immune depleted factor VIII deficient plasma showed that the DRVT ratio increased when the factor VIII concentration fell below 0.15 IU/ml. There was no significant association between plasma factor VIII concentration and positive DRVT results in haemophiliacs. The addition of porcine factor VIII concentrate produced no correction in eight of the 12 with DRVTs indicative of lupus anticoagulant, suggesting that these were prolonged by antiphospholipid activity. It is concluded that the presence of lupus anticoagulant and anticardiolipin antibodies in haemophiliacs may represent an antiphospholipid response to viraemic challenge, not only to HIV but also to other viral antigens, and that a very low factor VIII concentration may produce a false positive DRVT result. PMID:2500459

Areas of improvement in anticoagulant safety. Data from the CACAO study, a cohort in general practice

PubMed Central

Cogneau, Joël; Gaboreau, Yoann; Abenhaïm, Nathan; Bayen, Marc; Calafiore, Matthieu; Guichard, Claude; Jacquet, Jean-Pierre; Lacoin, François; Bertoletti, Laurent

2017-01-01

Background Real-world studies on anticoagulants are mostly performed on health insurance databases, limited to reported events, and sometimes far from every-day issues in family practice. We assess the presence of data for safe monitoring of oral anticoagulants in general practice, and compare patients’ knowledge of taking an anticoagulant between vitamin K antagonists (VKA) and direct anticoagulants (DOAC), and the general practitioner’s perception of their adherence to anticoagulation. Methods The CACAO study is a national cohort study, conducted by general practitioners on ambulatory patients under oral anticoagulant. In the first phase, investigators provided safety data available from medical records at inclusion. They also evaluated patients’ knowledge about anticoagulation and graded their perception of patients’ adherence. Results Between April and December 2014, 463 general practitioners included 7154 patients. Renal and hepatic function tests were respectively unavailable in 109 (7.5%) and 359 (24.7%) DOAC patients. Among patients with atrial fibrillation, 345 patients (6.9%) had a questionable indication of anticoagulant (CHA2DS2-Vasc<2). One hundred and thirty-three VKA patients (2.3%) and 70 DOAC patients (4.9%) answered they took no anticoagulant (p<0.0001). According to general practitioners’ perception, 430 patients (6.1%) were classified as “not very” or “not adherent”, with no difference between groups. Conclusions Our results highlight the efforts needed to improve anticoagulant safety in daily practice: decreasing the rate of unknown biological data in patients with DOACs or the rate of patients with VKA with no strong indication of anticoagulation, and improving patient knowledge with regard to their anticoagulant. Patients’ adherence seems highly over-estimated by the general practitioners. Clinical trial registration ClinicalTrials.gov NCT02376777 PMID:28384199

A Multilevel Analysis of Real-World Variations in Oral Anticoagulation Initiation for Atrial Fibrillation in Valencia, a European Region

PubMed Central

García-Sempere, Aníbal; Bejarano-Quisoboni, Daniel; Librero, Julián; Rodríguez-Bernal, Clara L.; Peiró, Salvador; Sanfélix-Gimeno, Gabriel

2017-01-01

Introduction: Beyond clinical trials, clinical practice guidelines, and administrative regulation, treatment decision-making can be influenced by individual and contextual factors. Our goal was to describe variations in the patterns of initiation of anticoagulation therapy in patients with atrial fibrillation by Health Areas (HA) in the region of Valencia in Spain and to quantify the influence of the HAs on variations in treatment choice. Methods: We conducted a population-based retrospective cohort study of all atrial fibrillation patients who started treatment with oral anticoagulants between November 2011 and February 2014 in each of the region's 24 HAs. We described patient and utilization characteristics per HA and initiation patterns over time, and we identified contextual and individual factors associated with differences in initiation patterns. Results: 21,879 patients initiated treatment with an oral anticoagulant in the 24 HAs. Initiation with direct oral anticoagulants (DOAC) in the first year was 14.6%. In November 2013 the ratio was 25.4%, with HA ratios ranging from 3.8 to 57.1%. DOAC-initiating patients had less comorbidity but were more likely to present episodes of previous ischemic stroke, hemorrhagic stroke, or TIA when compared with patients initiating with VKA treatment. Variability among HAs was statistically significant, with the majority of HAs ranking above or below the regional initiation average (ICC ≈ 8%). Conclusion: There was high variability in the percentage of DOAC initiation and in the choice of DOAC among HAs. Interventions aimed to improve DOAC initiation decision-making and to reduce variations should take into account the Health Area component. PMID:28883793

A Multilevel Analysis of Real-World Variations in Oral Anticoagulation Initiation for Atrial Fibrillation in Valencia, a European Region.

PubMed

García-Sempere, Aníbal; Bejarano-Quisoboni, Daniel; Librero, Julián; Rodríguez-Bernal, Clara L; Peiró, Salvador; Sanfélix-Gimeno, Gabriel

2017-01-01

Introduction: Beyond clinical trials, clinical practice guidelines, and administrative regulation, treatment decision-making can be influenced by individual and contextual factors. Our goal was to describe variations in the patterns of initiation of anticoagulation therapy in patients with atrial fibrillation by Health Areas (HA) in the region of Valencia in Spain and to quantify the influence of the HAs on variations in treatment choice. Methods: We conducted a population-based retrospective cohort study of all atrial fibrillation patients who started treatment with oral anticoagulants between November 2011 and February 2014 in each of the region's 24 HAs. We described patient and utilization characteristics per HA and initiation patterns over time, and we identified contextual and individual factors associated with differences in initiation patterns. Results: 21,879 patients initiated treatment with an oral anticoagulant in the 24 HAs. Initiation with direct oral anticoagulants (DOAC) in the first year was 14.6%. In November 2013 the ratio was 25.4%, with HA ratios ranging from 3.8 to 57.1%. DOAC-initiating patients had less comorbidity but were more likely to present episodes of previous ischemic stroke, hemorrhagic stroke, or TIA when compared with patients initiating with VKA treatment. Variability among HAs was statistically significant, with the majority of HAs ranking above or below the regional initiation average (ICC ≈ 8%). Conclusion: There was high variability in the percentage of DOAC initiation and in the choice of DOAC among HAs. Interventions aimed to improve DOAC initiation decision-making and to reduce variations should take into account the Health Area component.

[Characterisation of thromboembolic risk in a mexican population with non-valvular atrial fibrillation and its effect on anticoagulation (MAYA Study)].

PubMed

Vázquez-Acosta, Jorge A; Ramírez-Gutiérrez, Álvaro E; Cerecedo-Rosendo, Mario A; Olivera-Barrera, Francisco M; Tenorio-Sánchez, Salvador S; Nieto-Villarreal, Javier; González-Borjas, José M; Villanueva-Rodríguez, Estefanie

2016-01-01

To evaluate the risk of stroke and bleeding using the CHA2DS2-VASc and HAS-BLED scores in Mexican patients with atrial fibrillation and to analyze whether the risk score obtained determined treatment decisions regarding antithrombotic therapy. This is an observational, retrospective study in Mexican patients recently diagnosed with atrial fibrillation. The risk of stroke was assessed using the CHA2DS2-VASc scores. The bleeding risk was evaluated using the HAS-BLED score. The frequency of use of antithrombotic therapy was calculated according to the results of the score risk assessment. A total of 350 patients with non-valvular atrial fibrillation were analyzed. A 92.9% of patients had a high risk (score ≥ 2) of stroke according to the CHA2DS2-VASc score and only 17.2% were treated with anticoagulants. A high proportion of patients with atrial fibrillation (72.5%) showed both a high risk of stroke and a high risk of bleeding based on HAS-BLED score. In this group of patients with atrial fibrillation, from Northeast Mexico, there is a remarkably underutilization of anticoagulation despite the high risk of stroke of these patients.

A new instrument for measuring anticoagulation-related quality of life: development and preliminary validation

PubMed Central

Samsa, Greg; Matchar, David B; Dolor, Rowena J; Wiklund, Ingela; Hedner, Ewa; Wygant, Gail; Hauch, Ole; Marple, Cheryl Beadle; Edwards, Roger

2004-01-01

Background Anticoagulation can reduce quality of life, and different models of anticoagulation management might have different impacts on satisfaction with this component of medical care. Yet, to our knowledge, there are no scales measuring quality of life and satisfaction with anticoagulation that can be generalized across different models of anticoagulation management. We describe the development and preliminary validation of such an instrument – the Duke Anticoagulation Satisfaction Scale (DASS). Methods The DASS is a 25-item scale addressing the (a) negative impacts of anticoagulation (limitations, hassles and burdens); and (b) positive impacts of anticoagulation (confidence, reassurance, satisfaction). Each item has 7 possible responses. The DASS was administered to 262 patients currently receiving oral anticoagulation. Scales measuring generic quality of life, satisfaction with medical care, and tendency to provide socially desirable responses were also administered. Statistical analysis included assessment of item variability, internal consistency (Cronbach's alpha), scale structure (factor analysis), and correlations between the DASS and demographic variables, clinical characteristics, and scores on the above scales. A follow-up study of 105 additional patients assessed test-retest reliability. Results 220 subjects answered all items. Ceiling and floor effects were modest, and 25 of the 27 proposed items grouped into 2 factors (positive impacts, negative impacts, this latter factor being potentially subdivided into limitations versus hassles and burdens). Each factor had a high degree of internal consistency (Cronbach's alpha 0.78–0.91). The limitations and hassles factors consistently correlated with the SF-36 scales measuring generic quality of life, while the positive psychological impact scale correlated with age and time on anticoagulation. The intra-class correlation coefficient for test-retest reliability was 0.80. Conclusions The DASS has

Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation.

PubMed

Fang, Margaret C; Chang, Yuchiao; Hylek, Elaine M; Rosand, Jonathan; Greenberg, Steven M; Go, Alan S; Singer, Daniel E

2004-11-16

The risk for atrial fibrillation-associated stroke increases at low anticoagulation intensities. However, higher intensities increase hemorrhage risk. Optimal use of warfarin for atrial fibrillation requires precise information on the risk for intracranial hemorrhage as a function of patient age and anticoagulation intensity. To examine the relationship of age, anticoagulation intensity, and risk for intracranial hemorrhage. Case-control study. Academic medical center. 170 case-patients who developed intracranial hemorrhage during warfarin therapy and 1020 matched controls who did not; both case-patients and controls were taking warfarin for atrial fibrillation. The authors performed multivariable conditional logistic regression to determine the odds of intracranial hemorrhage with regard to age and international normalized ratio (INR), controlling for comorbid conditions and aspirin use. Case-patients were older than controls (median age, 78 years vs. 75 years; P < 0.001) and had higher median INRs (2.7 vs. 2.3; P < 0.001). The risk for intracranial hemorrhage increased at 85 years of age or older (adjusted odds ratio, 2.5 [95% CI, 1.3 to 4.7]; referent age, 70 to 74 years) and at an INR range of 3.5 to 3.9 (adjusted odds ratio, 4.6 [CI, 2.3 to 9.4]; referent INR, 2.0 to 3.0). The risk for intracranial hemorrhage at INRs less than 2.0 did not differ statistically from the risk at INRs of 2.0 to 3.0 (adjusted odds ratio, 1.3 [CI, 0.8 to 2.2]). Although duration of anticoagulation has been associated with hemorrhage in other studies, the current study could not control for this potential confounder. The risk for intracranial hemorrhage increases at age 85 years. International normalized ratios less than 2.0 were not associated with lower risk for intracranial hemorrhage compared with INRs between 2.0 and 3.0. Therefore, anticoagulation management should focus on maintaining INRs in the 2.0 to 3.0 range, even in elderly patients with atrial fibrillation, rather than

Post-polypectomy bleeding and thromboembolism risks associated with warfarin vs direct oral anticoagulants.

PubMed

Yanagisawa, Naohiro; Nagata, Naoyoshi; Watanabe, Kazuhiro; Iida, Tatsuhiro; Hamada, Mariko; Kobayashi, Sakurako; Shimbo, Takuro; Akiyama, Junichi; Uemura, Naomi

2018-04-14

To verify the validity of the endoscopy guidelines for patients taking warfarin or direct oral anticoagulants (DOAC). We collected data from 218 patients receiving oral anticoagulants (73 DOAC users, 145 warfarin users) and 218 patients not receiving any antithrombotics (age- and sex-matched controls) who underwent polypectomy. (1) We evaluated post-polypectomy bleeding (PPB) risk in patients receiving warfarin or DOAC compared with controls; (2) we assessed the risks of PPB and thromboembolism between three AC management methods: Discontinuing AC with heparin bridge (HPB) (endoscopy guideline recommendation), continuing AC, and discontinuing AC without HPB. PPB rate was significantly higher in warfarin users and DOAC users compared with controls (13.7% and 13.7% vs 0.9%, P < 0.001), but was not significantly different between rivaroxaban (13.2%), dabigatran (11.1%), and apixaban (13.3%) users. Two thromboembolic events occurred in warfarin users, but none in DOAC users. Compared with the continuing anticoagulant group, the discontinuing anticoagulant with HPB group (guideline recommendation) had a higher PPB rate (10.8% vs 19.6%, P = 0.087). These findings were significantly evident in warfarin but not DOAC users. One thrombotic event occurred in the discontinuing anticoagulant with HPB group and the discontinuing anticoagulant without HPB group; none occurred in the continuing anticoagulant group. PPB risk was similar between patients taking warfarin and DOAC. Thromboembolism was observed in warfarin users only. The guideline recommendations for HPB should be re-considered.

Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass.

PubMed

Gunaratne, Ruwan; Kumar, Shekhar; Frederiksen, James W; Stayrook, Steven; Lohrmann, Jens L; Perry, Kay; Bompiani, Kristin M; Chabata, Charlene V; Thalji, Nabil K; Ho, Michelle D; Arepally, Gowthami; Camire, Rodney M; Krishnaswamy, Sriram; Sullenger, Bruce A

2018-06-04

Unfractionated heparin (UFH), the standard anticoagulant for cardiopulmonary bypass (CPB) surgery, carries a risk of post-operative bleeding and is potentially harmful in patients with heparin-induced thrombocytopenia-associated antibodies. To improve the activity of an alternative anticoagulant, the RNA aptamer 11F7t, we solved X-ray crystal structures of the aptamer bound to factor Xa (FXa). The finding that 11F7t did not bind the catalytic site suggested that it could complement small-molecule FXa inhibitors. We demonstrate that combinations of 11F7t and catalytic-site FXa inhibitors enhance anticoagulation in purified reaction mixtures and plasma. Aptamer-drug combinations prevented clot formation as effectively as UFH in human blood circulated in an extracorporeal oxygenator circuit that mimicked CPB, while avoiding side effects of UFH. An antidote could promptly neutralize the anticoagulant effects of both FXa inhibitors. Our results suggest that drugs and aptamers with shared targets can be combined to exert more specific and potent effects than either agent alone.

Anticoagulant and antithrombotic drugs in pregnancy: what are the anesthetic implications for labor and cesarean delivery?

PubMed

Butwick, A J; Carvalho, B

2011-02-01

Neuraxial anesthetic techniques are commonly used during the peripartum period to provide effective pain relief for labor and anesthesia during cesarean delivery. Major neurologic complications are rare after neuraxial anesthesia; however, spinal hematoma is associated with catastrophic neurologic outcomes (including lower-limb paralysis). Anticoagulant and antithrombotic drugs can increase the risk of spinal hematoma after neuraxial anesthesia, and better understanding of the pharmacokinetics and pharmacodynamics of anticoagulants has led to greater appreciation for withholding anticoagulation before and after neuraxial anesthesia. A number of national anesthetic societies have produced guidelines for performing neuraxial anesthesia in patients receiving anticoagulation. However, there is limited information about anesthetic implications of anticoagulation during the peripartum period. This article will review the risks of spinal hematoma after neuraxial anesthesia in pregnant patients; current guidelines for neuraxial anesthesia for anticoagulated patients; and relevant pharmacological data of specific anticoagulant and antithrombotic drugs in pregnancy.

Outcomes and costs of left atrial appendage closure from randomized controlled trial and real-world experience relative to oral anticoagulation.

PubMed

Panikker, Sandeep; Lord, Joanne; Jarman, Julian W E; Armstrong, Shannon; Jones, David G; Haldar, Shouvik; Butcher, Charles; Khan, Habib; Mantziari, Lilian; Nicol, Edward; Hussain, Wajid; Clague, Jonathan R; Foran, John P; Markides, Vias; Wong, Tom

2016-12-07

The aim of this study was to analyse randomized controlled study and real-world outcomes of patients with non-valvular atrial fibrillation (NVAF) undergoing left atrial appendage closure (LAAC) with the Watchman device and to compare costs with available antithrombotic therapies. Registry data of LAAC from two centres were prospectively collected from 110 patients with NVAF at risk of stroke, suitable and unsuitable for long-term anticoagulation (age 71.3 ± 9.2 years, CHADS 2 2.8 ± 1.2, CHA 2 DS 2 -VASc 4.5 ± 1.6, and HAS-BLED 3.8 ± 1.1). Outcomes from PROTECT AF and registry study LAAC were compared with warfarin, dabigatran, rivaroxaban, apixaban, aspirin, and no treatment using a network meta-analysis. Costs were estimated over a 10-year horizon. Uncertainty was assessed using sensitivity analyses. The procedural success rate was 92% (103/112). Follow-up was 24.1 ± 4.6 months, during which annual rates of stroke, major bleeding, and all-cause mortality were 0.9% (2/223 patient-years), 0.9% (2/223 patient-years), and 1.8% (4/223 patient-years), respectively. Anticoagulant therapy was successfully stopped in 91.2% (93/102) of implanted patients by 12 months. Registry study LAAC stroke and major bleeding rates were significantly lower than PROTECT AF results: mean absolute difference of stroke, 0.89% (P = 0.02) and major bleeding, 5.48% (P < 0.001). Left atrial appendage closure achieved cost parity between 4.9 years vs. dabigatran 110 mg and 8.4 years vs. warfarin. At 10 years, LAAC was cost-saving against all therapies (range £1162-£7194). Left atrial appendage closure in NVAF in a real-world setting may result in lower stroke and major bleeding rates than reported in LAAC clinical trials. Left atrial appendage closure in both settings achieves cost parity in a relatively short period of time and may offer substantial savings compared with current therapies. Savings are most pronounced among higher risk patients and those unsuitable for anticoagulation

Outcomes and costs of left atrial appendage closure from randomized controlled trial and real-world experience relative to oral anticoagulation

PubMed Central

Panikker, Sandeep; Lord, Joanne; Jarman, Julian W.E.; Armstrong, Shannon; Jones, David G.; Haldar, Shouvik; Butcher, Charles; Khan, Habib; Mantziari, Lilian; Nicol, Edward; Hussain, Wajid; Clague, Jonathan R.; Foran, John P.; Markides, Vias; Wong, Tom

2016-01-01

Aims The aim of this study was to analyse randomized controlled study and real-world outcomes of patients with non-valvular atrial fibrillation (NVAF) undergoing left atrial appendage closure (LAAC) with the Watchman device and to compare costs with available antithrombotic therapies. Methods and results Registry data of LAAC from two centres were prospectively collected from 110 patients with NVAF at risk of stroke, suitable and unsuitable for long-term anticoagulation (age 71.3 ± 9.2 years, CHADS2 2.8 ± 1.2, CHA2DS2-VASc 4.5 ± 1.6, and HAS-BLED 3.8 ± 1.1). Outcomes from PROTECT AF and registry study LAAC were compared with warfarin, dabigatran, rivaroxaban, apixaban, aspirin, and no treatment using a network meta-analysis. Costs were estimated over a 10-year horizon. Uncertainty was assessed using sensitivity analyses. The procedural success rate was 92% (103/112). Follow-up was 24.1 ± 4.6 months, during which annual rates of stroke, major bleeding, and all-cause mortality were 0.9% (2/223 patient-years), 0.9% (2/223 patient-years), and 1.8% (4/223 patient-years), respectively. Anticoagulant therapy was successfully stopped in 91.2% (93/102) of implanted patients by 12 months. Registry study LAAC stroke and major bleeding rates were significantly lower than PROTECT AF results: mean absolute difference of stroke, 0.89% (P = 0.02) and major bleeding, 5.48% (P < 0.001). Left atrial appendage closure achieved cost parity between 4.9 years vs. dabigatran 110 mg and 8.4 years vs. warfarin. At 10 years, LAAC was cost-saving against all therapies (range £1162–£7194). Conclusion Left atrial appendage closure in NVAF in a real-world setting may result in lower stroke and major bleeding rates than reported in LAAC clinical trials. Left atrial appendage closure in both settings achieves cost parity in a relatively short period of time and may offer substantial savings compared with current therapies. Savings are most pronounced among higher risk patients and those

Parallel determination of gut permeability in man with M(r) 400, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol.

PubMed

Parlesak, A; Bode, J C; Bode, C

1994-11-01

Polyethylene glycol has been in use for a number of years for the assessment of gut permeability. The methods so far employed are usually limited to polyethylene glycols in the low relative molecular mass range (up to M(r) 1300). We developed a method for the simultaneous determination of gut permeability to M(r) 400, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol, by applying a single oral dose of an appropriate mixture of these polyethylene glycols. After extraction from 24 h-urine, M(r) 1500, M(r) 4000 and M(r) 10,000 polyethylene glycol were quantified by size exclusion chromatography, while M(r) 400 polyethylene glycol was determined by reversed phase chromatography. The detection limit of polyethylene glycol in the relative molecular mass range between M(r) 1500 and M(r) 10,000 was found to be 0.2 mg/l urine, and the detection limit of M(r) 400 polyethylene glycol 5 mg/l urine. Recovery of the polyethylene glycols (N = 6) were 86.6% (CV: 4.8%) for M(r) 400, 94.1% (CV: 7.2%) for M(r) 1500, 97.1% (CV: 5.5%) for M(r) 4000 and 97.4% (CV: 5.6%) for M(r) 10,000. No significant difference was found between the excretion rates in 24 h-urine of M(r) 400 and M(r) 1500 polyethylene glycols in patients with Crohn's disease (M(r) 400: 34.4 +/- 5.5%; M(r) 1500: 5.22 +/- 2.27%; mean +/- SEM, N = 10) and healthy controls (M(r) 400: 33.6 +/- 3.2%, M(r) 1500: 1.09 +/- 0.26%; N = 21). The excretion rate of M(r) 4000 polyethylene glycol was markedly higher in patients with Crohn's disease (0.462 +/- 0.177%) than in healthy controls (0.049 +/- 0.012%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Oral Anticoagulation in Chronic Kidney Disease and Atrial Fibrillation.

PubMed

Heine, Gunnar H; Brandenburg, Vincent; Schirmer, Stephan H

2018-04-27

Cardiological societies recommend, in their guidelines, that patients with atrial fibrillation and an intermediate (or higher) risk of stroke and systemic embolization should be treated with oral anticoagulant drugs. For patients who do not have mitral valve stenosis or a mechanical valve prosthesis, non-vitamin-K dependent oral anticoagulants (NOAC) are preferred over vitamin K antagonists (VKA) for this purpose. It is unclear, however, whether patients with chronic kidney disease and atrial fibrillation benefit from oral anticoagulation to the same extent as those with normal kidney function. It is also unclear which of the two types of anti - coagulant drug is preferable for patients with chronic kidney disease; NOAC are, in part, renally eliminated. This review is based on pertinent publications retrieved by a selective literature search, and on international guidelines. Current evidence suggests that patients with atrial fibrillation who have chronic kidney disease with a glomerular filtration rate (GFR) above 15 mL/ min/1.73 m² should be treated with an oral anticoagulant drug if they have an at least intermediate risk of embolization, as assessed with the CHA2DS2-VASc score. For patients with advanced chronic kidney disease (GFR from 15 to 29 mL/ min/1.73 m²), however, this recommendation is based only on registry studies. For dialysis patients with atrial fibrillation, decisions whether to give oral anticoagulant drugs should be taken on an individual basis, in view of the elevated risk of hemorrhage and the unclear efficacy of such drugs in these patients. The subgroup analyses of the NOAC approval studies show that, for patients with atrial fibrillation and chronic kidney disease with a creatinine clearance of >25-30 mL/min, NOAC should be given in preference to VKA, as long as the patient does not have mitral valve stenosis or a mechanical valve prosthesis. For those whose creatinine clearance is less than 25 mL/min, the relative merits of NOAC versus

Quantitative evaluation of multi-parametric MR imaging marker changes post-laser interstitial ablation therapy (LITT) for epilepsy

NASA Astrophysics Data System (ADS)

Tiwari, Pallavi; Danish, Shabbar; Wong, Stephen; Madabhushi, Anant

2013-03-01

Laser-induced interstitial thermal therapy (LITT) has recently emerged as a new, less invasive alternative to craniotomy for treating epilepsy; which allows for focussed delivery of laser energy monitored in real time by MRI, for precise removal of the epileptogenic foci. Despite being minimally invasive, the effects of laser ablation on the epileptogenic foci (reflected by changes in MR imaging markers post-LITT) are currently unknown. In this work, we present a quantitative framework for evaluating LITT-related changes by quantifying per-voxel changes in MR imaging markers which may be more reflective of local treatment related changes (TRC) that occur post-LITT, as compared to the standard volumetric analysis which involves monitoring a more global volume change across pre-, and post-LITT MRI. Our framework focuses on three objectives: (a) development of temporal MRI signatures that characterize TRC corresponding to patients with seizure freedom by comparing differences in MR imaging markers and monitoring them over time, (b) identification of the optimal time point when early LITT induced effects (such as edema and mass effect) subside by monitoring TRC at subsequent time-points post-LITT, and (c) identification of contributions of individual MRI protocols towards characterizing LITT-TRC for epilepsy by identifying MR markers that change most dramatically over time and employ individual contributions to create a more optimal weighted MP-MRI temporal profile that can better characterize TRC compared to any individual imaging marker. A cohort of patients were monitored at different time points post-LITT via MP-MRI involving T1-w, T2-w, T2-GRE, T2-FLAIR, and apparent diffusion coefficient (ADC) protocols. Post affine registration of individual MRI protocols to a reference MRI protocol pre-LITT, differences in individual MR markers are computed on a per-voxel basis, at different time-points with respect to baseline (pre-LITT) MRI as well as across subsequent time

Endoscopic diode laser therapy for chronic radiation proctitis.

PubMed

Polese, Lino; Marini, Lucia; Rizzato, Roberto; Picardi, Edgardo; Merigliano, Stefano

2018-01-01

The purpose of this study is to determine the effectiveness of endoscopic diode laser therapy in patients presenting rectal bleeding due to chronic radiation proctitis (CRP). A retrospective analysis of CRP patients who underwent diode laser therapy in a single institution between 2010 and 2016 was carried out. The patients were treated by non-contact fibers without sedation in an outpatient setting. Fourteen patients (median age 77, range 73-87 years) diagnosed with CRP who had undergone high-dose radiotherapy for prostatic cancer and who presented with rectal bleeding were included. Six required blood transfusions. Antiplatelet (three patients) and anticoagulant (two patients) therapy was not suspended during the treatments. The patients underwent a median of two sessions; overall, a mean of 1684 J of laser energy per session was used. Bleeding was resolved in 10/14 (71%) patients, and other two patients showed improvement (93%). Only one patient, who did not complete the treatment, required blood transfusions after laser therapy; no complications were noted during or after the procedures. Study findings demonstrated that endoscopic non-contact diode laser treatment is safe and effective in CRP patients, even in those receiving antiplatelet and/or anticoagulant therapy.

What Are Anticoagulants and Antiplatelet Agents?

MedlinePlus

... activated partial thromboplastin time (aPTT) test. • Never take aspirin with anticoagulants unless your doctor tells you to. • ... before taking other medicines or supplements, such as aspirin, vitamins, cold medicine, pain medicine, sleeping pills or ...

Preemptive Anticoagulation in Patients With a High Pretest Probability of Pulmonary Embolism: Are Guidelines Followed?

PubMed

Willoughby, Laura; Adams, Daniel M; Evans, R Scott; Lloyd, James F; Stevens, Scott M; Woller, Scott C; Bledsoe, Joseph R; Aston, Valerie T; Wilson, Emily L; Elliott, C Gregory

2018-05-01

Guidelines suggest anticoagulation of patients with high pretest probability of pulmonary embolism (PE) while awaiting diagnostic test results (preemptive anticoagulation). Data relevant to the practice of preemptive anticoagulation are not available. We reviewed 3,500 consecutive patients who underwent CT pulmonary angiography (CTPA) at two EDs. We classified the pretest probability for PE using the revised Geneva Score (RGS) as low (RGS 0-3), intermediate (RGS 4-10), or high (RGS 11-18). We classified patients with a high pretest probability of PE as receiving preemptive anticoagulation if therapeutic anticoagulation was given before CTPA completion. Patients with a high bleeding risk and those receiving treatment for DVT before CTPA were excluded from the preemptive anticoagulation analysis. We compared the time elapsed between ED registration and CTPA completion for patients with a low, intermediate, and high pretest probability for PE. We excluded three of 3,500 patients because CTPA preceded ED registration. Of the remaining 3,497 patients, 167 (4.8%) had a high pretest probability for PE. After excluding 29 patients for high bleeding risk and 21 patients who were treated for DVT prior to CTPA, only two of 117 patients (1.7%) with a high pretest probability for PE received preemptive anticoagulation. Furthermore, 37 of the remaining 115 patients (32%) with a high pretest probability for PE had a preexisting indication for anticoagulation but did not receive preemptive anticoagulation. The time from ED registration to CTPA completion did not differ based on the pretest probability of PE. Physicians rarely use preemptive anticoagulation in patients with a high pretest probability for PE. Clinicians do not expedite CTPA examinations for patients with a high pretest probability for PE. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Anticoagulation Use and Clinical Outcomes Following Major Bleeding on Dabigatran or Warfarin in Atrial Fibrillation

PubMed Central

Hernandez, Inmaculada; Zhang, Yuting; Brooks, Maria M.; Chin, Paul K.L.; Saba, Samir

2016-01-01

Background and Purpose Little is known about the clinical outcomes associated with post-hemorrhage anticoagulation resumption for atrial fibrillation. This study had two objectives: first, to evaluate anticoagulation use after a first major bleed on warfarin or dabigatran; and second, to compare effectiveness and safety outcomes between patients discontinuing anticoagulation after a major bleed and patients restarting warfarin or dabigatran. Methods Using 2010-2012 Medicare Part D data, we identified atrial fibrillation patients who experienced a major bleeding event while using warfarin (n=1135) or dabigatran (n=404) and categorized them by their post-hemorrhage use of anticoagulation. We followed them until an ischemic stroke, recurrent hemorrhage, or death through December 31, 2012. We constructed logistic regression models to evaluate factors impacting anticoagulation resumption, and Cox Proportional Hazard models to compare the combined risk of ischemic stroke and all-cause mortality, and the risk of recurrent bleeding between treatment groups. Results Resumption of anticoagulation with warfarin (hazard ratio (HR) 0.76; 95%CI, 0.59-0.97) or dabigatran (HR0.66; 95%CI 0.44-0.99) was associated with lower combined risk of ischemic stroke and all-cause mortality than anticoagulation discontinuation. The incidence of recurrent major bleeding was higher for patients prescribed warfarin after the event than for those prescribed dabigatran (HR2.31; 95%CI, 1.19-4.76) or whose anticoagulation ceased (HR1.56; 95%CI, 1.10-2.22), but did not differ between patients restarting dabigatran and those discontinuing anticoagulation (HR0.66; 95% CI, 0.32-1.33). Conclusions Dabigatran was associated with a superior benefit/risk ratio than warfarin and anticoagulation discontinuation in the treatment of atrial fibrillation patients who have survived a major bleed. PMID:27909200

International Normalized Ratio values in group versus individual appointments in a pharmacist-managed anticoagulation clinic.

PubMed

Griffin, Brooke L; Burkiewicz, Jill S; Peppers, Laura R; Warholak, Terri L

2009-07-01

The clinical effectiveness of a group-visit model versus individual point-of-care visits is compared by International Normalized Ratio (INR) monitoring in a pharmacist-managed anticoagulation clinic. This study was a prospective, randomized, repeated-measures, two-group, intention-to-treat comparison and survey at a pharmacist-managed anticoagulation clinic in a managed-care ambulatory care setting. Patients were eligible for this study if they were taking warfarin therapy for at least 30 days, had a goal INR range, and provided consent. At a routine point-of-care visit, eligible patients were randomly invited to participate in group visits. The number of visits and INR values were documented prospectively for both groups during the 16-week study period. Of the 45 patients who consented and enrolled in group visits, 28 patients participated for the 16-week study period. The control group included 108 patients seen by a pharmacist for individual anticoagulation appointments. No significant difference in the percentage of INR values within the therapeutic range was detected between patients in the group-visit model versus patients receiving individual visits (59% versus 56.6%, respectively; p = 0.536). Seventy-three percent of INR values for patients who attended group visits were within +/- 0.2 of the desired INR range compared with 71.9% of those in the control group ( p = 0.994). In addition, 79% of group-visit patients were within the therapeutic range at their last clinic visit compared with 67% of patients who attended individual appointments (p = 0.225). Group visits were preferred by 51% (n = 38) of patients who completed the satisfaction survey. Of the 92 patients who declined group-visit participation, 36% indicated that the time of day that group visits were offered was inconvenient. There were no thromboembolic or hemorrhagic events documented in either group during the study period. Group visits in a pharmacist-managed anticoagulation clinic may provide